MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Neurobiology of Aging' source. Wed, 08 Feb 2012 16:54:28 +0100 http://www.medworm.com/index.php?rid=5663501&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300950%26dopt%3DAbstract Authors: Proitsi P, Lupton MK, Dudbridge F, Tsolaki M, Hamilton G, Daniilidou M, Pritchard M, Lord K, Martin BM, Craig D, Todd S, McGuinness B, Hollingworth P, Harold D, Kloszewska I, Soininen H, Mecocci P, Velas B, Gill M, Lawlor B, Rubinsztein DC, Brayne C, Passmore PA, Williams J, Lovestone S, Powell JF Abstract Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-re... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663501 Tue, 31 Jan 2012 05:00:00 +0100 5663501 http://www.medworm.com/index.php?rid=5663500&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300951%26dopt%3DAbstract Authors: Tanaka C, Coling DE, Manohar S, Chen GD, Hu BH, Salvi R, Henderson D Abstract The biological mechanisms that give rise to age-related hearing loss (ARHL) are still poorly understood. However, there is growing recognition that oxidative stress may be an important factor. To address this issue, we measured the changes in the expression of cochlear oxidative stress and antioxidant defense-related genes in young (2 months old), middle-aged (12 months old), and old (21-25 months old) Fischer 344/NHsd (F344/NHsd) rats and compared gene expression changes with ARHL. A quantitative real-time reverse transcription polymerase chain reaction array revealed a significant age-related downregulation of only 1 gene, stearoyl-coenzyme A desaturase 1, and upregulation of 12 genes: 24-dehyd... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663500 Tue, 31 Jan 2012 05:00:00 +0100 5663500 http://www.medworm.com/index.php?rid=5663499&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300952%26dopt%3DAbstract Authors: Hyodo K, Dan I, Suwabe K, Kyutoku Y, Yamada Y, Akahori M, Byun K, Kato M, Soya H Abstract A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (inc... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663499 Tue, 31 Jan 2012 05:00:00 +0100 5663499 http://www.medworm.com/index.php?rid=5663502&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22296644%26dopt%3DAbstract Authors: Grünewald A, Arns B, Seibler P, Rakovic A, Münchau A, Ramirez A, Sue CM, Klein C Abstract Mutations in ATP13A2 cause autosomal-recessive parkinsonism (Kufor-Rakeb syndrome; KRS). Because several other parkinsonism-associated proteins have been connected to mitochondrial function and mitophagy, we studied the impact of endogenous mutations in ATPase type 13A2 (ATP13A2) on mitochondria in fibroblasts from KRS patients compared with controls. In patients, we detected decreased adenosine triphosphate (ATP) synthesis rates, increased mitochondrial DNA levels, a higher frequency of mitochondrial DNA lesions, increased oxygen consumption rates, and increased fragmentation of the mitochondrial network. Importantly, overexpression of wild-type ATP13A2 rescued the respiration phen... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663502 Mon, 30 Jan 2012 05:00:00 +0100 5663502 http://www.medworm.com/index.php?rid=5663503&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285759%26dopt%3DAbstract In this study, we characterized the age-related changes in C. elegans male mating behavior to determine possible causes that ultimately lead to age-related muscle frailty. Unlike the kinetics of general behavioral decline, we found that mating behavior deteriorates early in adulthood, with no obvious muscle fiber disorganization or sperm dysfunction. Through direct mating behavior observations, Ca(2+) imaging, and pharmacological tests, we found that the muscular components used for mating become more excitable as the males age. Interestingly, manipulating either the expression of acetylcholine receptor (AChR) genes or dietary-mediated ether-a-go-go family K(+) channel function can reduce the muscle excitability of older males and concurrently improve mating behavior, suggesting a correlat... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663503 Fri, 27 Jan 2012 05:00:00 +0100 5663503 http://www.medworm.com/index.php?rid=5663505&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285757%26dopt%3DAbstract We examined the combined effect of plasma lipids/hypertension and apolipoprotein E (APOE) genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), APOE, and history of hypertension were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids/hypertension and cognitive function in apolipoprotein E4 allele (APOE4) carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma APOE levels in both E4- and E4+, and HDL level in E4-. The combination of hypertension and E4+, but not E4-, was associated with ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663505 Thu, 26 Jan 2012 05:00:00 +0100 5663505 http://www.medworm.com/index.php?rid=5663504&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285758%26dopt%3DAbstract Authors: He J, Carmichael O, Fletcher E, Singh B, Iosif AM, Martinez O, Reed B, Yonelinas A, Decarli C Abstract Age-related memory decline is the consequence of multiple biological factors that lead to brain structural and functional change, including gray matter atrophy, white matter injury, and loss of functional coordination between regions. However, the independent roles that each of these brain changes play in mediating memory decline is not clear. Therefore, we used magnetic resonance imaging (MRI) to measure gray matter (GM) volume, white matter hyperintensity (WMH) volumes, and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging-based functional connectivity among default mode network nodes in 76 cognitive normal older adults. We found that GM, WMH, an... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663504 Thu, 26 Jan 2012 05:00:00 +0100 5663504 http://www.medworm.com/index.php?rid=5663508&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22284987%26dopt%3DAbstract Authors: Shan L, Bossers K, Unmehopa U, Bao AM, Swaab DF Abstract Histamine is produced by the hypothalamic tuberomamillary nucleus (TMN). We studied its involvement in Alzheimer's disease (AD) by in situ hybridization of histidine decarboxylase (HDC), the key enzyme of histamine production, in 9 AD patients and 9 controls. Additionally, messenger (m) RNA levels of the 4 histamine receptors (H(1-4)R) and of the enzyme involved in histamine metabolism, histamine methyltransferase (HMT), were determined by quantitative polymerase chain reaction (qPCR) in the prefrontal cortex (PFC) in the course of AD (n = 49). Moreover, alterations in glia markers were studied. HDC-mRNA levels in the TMN were unchanged in AD, despite of the reduced number of Nissl-stained neurons (p = 0.001). Howeve... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663508 Wed, 25 Jan 2012 05:00:00 +0100 5663508 http://www.medworm.com/index.php?rid=5663507&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22284988%26dopt%3DAbstract Authors: Puzzo D, Privitera L, Palmeri A Abstract One of the hot topics in Alzheimer's disease research field is the "amyloid hypothesis" postulating that the increase and deposition of beta-amyloid peptides (Aβ) is the main pathogenetic factor. However, antiamyloid-based therapies have so far been a failure and, most importantly, growing evidences suggest that Aβ has important physiologic functions. Based on our previous findings demonstrating that low concentrations of Aβ enhanced both synaptic plasticity and memory, whereas high concentrations induced the well-known impairment of cognition, here we show that Aβ acts on hippocampal long-term potentiation and reference memory drawing biphasic dose-response curves. This phenomenon, characterized by low-dose stimulation and high... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663507 Wed, 25 Jan 2012 05:00:00 +0100 5663507 http://www.medworm.com/index.php?rid=5663506&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22284989%26dopt%3DAbstract Authors: Randall AD, Booth C, Brown JT Abstract Cognitive decline occurs during normal aging and is likely to be reflected in the neurophysiological properties of neural circuits with key roles in cognition, for example those of the limbic system. To identify candidate neurophysiological changes we used patch clamp methods to compare the intrinsic excitability properties of hippocampal CA1 pyramidal neurons of mature adult (8-10 month) and aged (22-24 month) mice. Resting potential, input resistance, and the "sag" observed on injection of hyperpolarizing current were not age-dependent. In contrast, the patterns of spike firing observed with depolarizing current injections demonstrated the presence of an age-related hypoexcitability. Action potential waveform analysis revealed that ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663506 Wed, 25 Jan 2012 05:00:00 +0100 5663506 http://www.medworm.com/index.php?rid=5663512&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277261%26dopt%3DAbstract Authors: Migliaccio R, Agosta F, Scola E, Magnani G, Cappa SF, Pagani E, Canu E, Comi G, Falini A, Gorno-Tempini ML, Bartolomeo P, Filippi M Abstract Using diffusion tensor magnetic resonance imaging tractography, ventral (inferior longitudinal fasciculus) and fronto-occipital (inferior fronto-occipital fasciculus) and dorsal (fronto-parietal superior longitudinal fasciculus) visual pathways were assessed in 7 patients with posterior cortical atrophy (PCA), showing either predominantly ventral or additional dorsal cognitive deficits. Corpus callosum and corticospinal tracts were also studied. Gray and white matter atrophy was assessed using voxel-based morphometry. In all PCA patients, abnormal diffusivity indexes were found in bilateral inferior longitudinal fasciculus and inferio... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663512 Mon, 23 Jan 2012 05:00:00 +0100 5663512 http://www.medworm.com/index.php?rid=5663511&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277262%26dopt%3DAbstract This study opens the possibility of [18F]AV-45, coupled with microPET, to visualize and quantitatively measure amyloid deposits in the brains of living APP/PS1 mice. PMID: 22277262 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663511 Mon, 23 Jan 2012 05:00:00 +0100 5663511 http://www.medworm.com/index.php?rid=5663510&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277263%26dopt%3DAbstract Authors: O'Connell RG, Balsters JH, Kilcullen SM, Campbell W, Bokde AW, Lai R, Upton N, Robertson IH Abstract One of the most reliable psychophysiological markers of aging is a linear decrease in the amplitude of the P300 potential, accompanied by a more frontal topographical orientation, but the precise neural origins of these differences have yet to be explored. We acquired simultaneous electroencephalogram (EEG)/functional magnetic resonance imaging (fMRI) recordings from 14 older and 15 younger adults who performed a 3-stimulus visual oddball task designed to elicit P3a and P3b components. As in previous reports, older adults had significantly reduced P3a/P3b amplitudes over parietal electrodes but larger amplitudes over frontal scalp with no between-group differences in accura... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663510 Mon, 23 Jan 2012 05:00:00 +0100 5663510 http://www.medworm.com/index.php?rid=5663509&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277264%26dopt%3DAbstract Authors: Zhang W, Bai M, Xi Y, Hao J, Zhang Z, Su C, Lei G, Miao J, Li Z Abstract Increased accumulation of amyloid-beta peptide (Aβ) and neuroinflammation is known to exist within the Alzheimer's disease (AD) brain. However, it remains unclear which form of Aβ pathologies triggers neuroinflammation and whether increased neuroinflammation contributes to cognitive deficits in AD. In the present study we found that increased inflammatory responses might occur early in preplaque APPswe/PS1dE9 mice, and were significantly enhanced in both early- and late-plaque APPswe/PS1dE9 mice. Correlational analysis revealed that multiple inflammatory indexes significantly correlated with soluble Aβ level, rather than amyloid plaque burden or insoluble Aβ level, in APPswe/PS1dE9 mice. Moreover,... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5663509 Mon, 23 Jan 2012 05:00:00 +0100 5663509 http://www.medworm.com/index.php?rid=5626580&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264648%26dopt%3DAbstract Authors: Vos S, van Rossum I, Burns L, Knol D, Scheltens P, Soininen H, Wahlund LO, Hampel H, Tsolaki M, Minthon L, Handels R, L'italien G, van der Flier W, Aalten P, Teunissen C, Barkhof F, Blennow K, Wolz R, Rueckert D, Verhey F, Visser PJ Abstract Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (Aβ)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (L... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5626580 Thu, 19 Jan 2012 05:00:00 +0100 5626580 http://www.medworm.com/index.php?rid=5626581&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261556%26dopt%3DAbstract Authors: Storandt M, Head D, Fagan AM, Holtzman DM, Morris JC Abstract Relations among antecedent biomarkers of Alzheimer disease (AD) were evaluated using causal modeling; although correlation cannot be equated to causation, causation does require correlation. Individuals aged 43 to 89 years (N = 220) enrolled as cognitively normal controls in longitudinal studies had clinical and psychometric assessment, structural magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarkers, and brain amyloid imaging via positron emission tomography with Pittsburgh Compound B (PIB) obtained within 1 year. CSF levels of Aβ(42) and tau were minimally correlated, indicating they represent independent processes. Aβ(42), tau, and their interaction explained 60% of the variance in PIB. Eff... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5626581 Tue, 17 Jan 2012 05:00:00 +0100 5626581 http://www.medworm.com/index.php?rid=5594995&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011005306%2Fabstract%3Frss%3Dyes (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5594995 Mon, 16 Jan 2012 15:14:34 +0100 5594995 http://www.medworm.com/index.php?rid=5594942&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011005264%2Fabstract%3Frss%3Dyes (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5594942 Mon, 16 Jan 2012 15:14:34 +0100 5594942 http://www.medworm.com/index.php?rid=5626582&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257984%26dopt%3DAbstract This study suggests for the first time a direct link between age-related differences in interlimb coordination and the control of corticospinal inhibitory processes. PMID: 22257984 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5626582 Mon, 16 Jan 2012 05:00:00 +0100 5626582 http://www.medworm.com/index.php?rid=5607228&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244934%26dopt%3DAbstract Authors: Kwon MJ, Baek W, Ki CS, Kim HY, Koh SH, Kim JW, Kim SH Abstract About 5% of amyotrophic lateral sclerosis (ALS) cases are known to be familial (fALS) and mutations in SOD1 and other genes are found in more than 20% of fALS patients and in 2%-4% of apparently sporadic ALS (sALS) cases. However, there are few reports on the proportion of fALS and the frequency of mutations in Korean patients with ALS. We screened mutations in the SOD1, FUS, TARDBP, ANG, and OPTN genes in 258 consecutively enrolled Korean patients with ALS from October 2006 to November 2010. The frequency of fALS was estimated to be 3.5% (9/258), and mutations were identified in 88.9% (8/9) of fALS patients but only in 2.8% (7/249) of sALS patients. Seven fALS and 3 sALS patients had mutations in SOD1 gene wh... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607228 Fri, 13 Jan 2012 05:00:00 +0100 5607228 http://www.medworm.com/index.php?rid=5607227&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245316%26dopt%3DAbstract Authors: Wu WE, Gass A, Glodzik L, Babb JS, Hirsch J, Sollberger M, Achtnichts L, Amann M, Monsch AU, Gonen O Abstract We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker-the amino acid derivative N-acetylaspartate (NAA). To test this, we obtained the whole-brain and whole-head N-acetylaspartate concentrations (WBNAA and WHNAA) with proton magnetic resonance (MR) spectroscopy; and the fractional brain parenchyma volume (fBPV)-a metric of atrophy, by segmenting the magnetic resonance image (MRI) from 42 (18 male) healthy young (31.9 ± 5.8 years old) and 100 (64 male, 72.6 ± 7.3 years old) cognitively normal elderly. The 12.8 ± 1.9 mM WBNAA of the young was not significantly different from the 13.1 ± 3.1 mM in ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607227 Thu, 12 Jan 2012 05:00:00 +0100 5607227 http://www.medworm.com/index.php?rid=5607226&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245317%26dopt%3DAbstract Authors: German DC, Khobahy I, Pastor J, Kuro-O M, Liu X Abstract Klotho is a putative age-suppressing gene whose overexpression in mice results in extension of life span. The Klotho gene encodes a single-pass transmembrane protein whose extracellular domain is shed and released into blood, urine, and cerebrospinal fluid, potentially functioning as a humoral factor. The extracellular domain of Klotho has an activity that increases the expression of antioxidant enzymes and confers resistance to oxidative stress in cultured cells and in whole animals. The transmembrane form of the Klotho protein directly binds to multiple fibroblast growth factor receptors and modifies their ligand affinity and specificity. The purpose of the present study was to determine the precise cellular locali... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607226 Thu, 12 Jan 2012 05:00:00 +0100 5607226 http://www.medworm.com/index.php?rid=5607232&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244088%26dopt%3DAbstract This study evaluates the possibility in differentiating 39 FTD, 39 AD, and 39 controls (CTR) by means of power spectral analysis and standardized low resolution brain electromagnetic tomography (sLORETA) within delta, theta, alpha 1 and 2, beta 1, 2, and 3 frequency bands. Both analyses revealed in AD patients, relative to CTR, higher expression of diffuse delta/theta and lower central/posterior fast frequency (from alpha1 to beta2) bands. FTD patients showed diffuse increased theta power compared with CTR and lower delta relative to AD patients. Compared with FTD, AD patients showed diffuse higher theta power at spectral analysis and, at sLORETA, decreased alpha2 and beta1 values in central/temporal regions. Spectral analysis and sLORETA provided complementary information that might help ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607232 Wed, 11 Jan 2012 05:00:00 +0100 5607232 http://www.medworm.com/index.php?rid=5607231&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244089%26dopt%3DAbstract Authors: Jawaid A, Leske H, Neumann M PMID: 22244089 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607231 Wed, 11 Jan 2012 05:00:00 +0100 5607231 http://www.medworm.com/index.php?rid=5607230&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244090%26dopt%3DAbstract Authors: Wilson JK, Baran B, Pace-Schott EF, Ivry RB, Spencer RM Abstract Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 years), middle-aged (35-50 years), and older (51-70 years) adults without disordered sleep. During an initial session, conducted either in the morning or evening, participants learned a motor sequence and a list of word pairs. Memory tests were given twice, 12 and 24 hours after training, allowing us to analyze off-line consolidation after a break that included sleep or normal wake. Sleep-depende... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607230 Wed, 11 Jan 2012 05:00:00 +0100 5607230 http://www.medworm.com/index.php?rid=5607229&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244091%26dopt%3DAbstract Authors: Julien A S, Schraermeyer A U Abstract Lipofuscin is a cytologic hallmark of aging in metabolically active postmitotic cells including neurons, cardiac muscle cells, and the retinal pigment epithelium (RPE). High levels of lipofuscin are involved in the pathogenesis of age-related macular degeneration (AMD), the main cause of blindness in the elderly population in the western world. Degradation and exocytosis of lipofuscin by RPE cells have not been observed in vivo until now, and no drug is known to eliminate the intracellular amount of lipofuscin. Here, we show that in monkeys treated with a small molecule belonging to the tetrahydropyridoethers class (n = 36 of 48 monkeys), RPE cells significantly release lipofuscin. In 4 eyes, macrophages were detected which had taken u... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607229 Wed, 11 Jan 2012 05:00:00 +0100 5607229 http://www.medworm.com/index.php?rid=5607233&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22236372%26dopt%3DAbstract Authors: Schlee W, Leirer V, Kolassa S, Thurm F, Elbert T, Kolassa IT Abstract The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18-89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2-4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirm... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5607233 Mon, 09 Jan 2012 05:00:00 +0100 5607233 http://www.medworm.com/index.php?rid=5580208&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227006%26dopt%3DAbstract Authors: Parbery-Clark A, Anderson S, Hittner E, Kraus N Abstract Aging disrupts neural timing, reducing the nervous system's ability to precisely encode sound. Given that the neural representation of temporal features is strengthened with musical training in young adults, can musical training offset the negative impact of aging on neural processing? By comparing auditory brainstem timing in younger and older musicians and nonmusicians to a consonant-vowel speech sound /da/. we document a musician's resilience to age-related delays in neural timing. PMID: 22227006 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580208 Sat, 07 Jan 2012 05:00:00 +0100 5580208 http://www.medworm.com/index.php?rid=5580209&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227005%26dopt%3DAbstract Authors: Scott L, Feng J, Kiss T, Needle E, Atchison K, Kawabe TT, Milici AJ, Hajós-Korcsok E, Riddell D, Hajós M Abstract Transgenic mice are used to model increased brain amyloid-β (Aβ) and amyloid plaque formation reflecting Alzheimer's disease pathology. In our study hippocampal network oscillations, population spikes, and long-term potentiation (LTP) were recorded in APPswe/PS1dE9 (APP/PS1) and presenilin1 (PS1) transgenic and wild type mice at 2, 4, and 8 months of age under urethane anesthesia. Hippocampal theta oscillations elicited by brainstem stimulation were similar in wild type and PS1 mice at all age groups. In contrast, APP/PS1 mice showed an age-dependent decrease in hippocampal activity, characterized by a significant decline in elicited theta power and frequen... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580209 Fri, 06 Jan 2012 05:00:00 +0100 5580209 http://www.medworm.com/index.php?rid=5580207&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227007%26dopt%3DAbstract Authors: Teismann P, Sathe K, Bierhaus A, Leng L, Martin HL, Bucala R, Weigle B, Nawroth PP, Schulz JB Abstract Parkinson's disease (PD) is a common neurodegenerative disorder of unknown pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Oxidative stress, microglial activation and inflammatory responses seem to contribute to the pathogenesis. The receptor for advanced glycation endproducts (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules. The formation of advanced glycation end products (AGEs), the first ligand of RAGE identified, requires a complex series of reactions including nonenzymatic glycation and free radical reactions involving superoxide-radicals and hydrogen peroxide. Binding of RAGE ligands results ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580207 Fri, 06 Jan 2012 05:00:00 +0100 5580207 http://www.medworm.com/index.php?rid=5580212&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226487%26dopt%3DAbstract Authors: Begg DP, Sinclair AJ, Weisinger RS Abstract During heat waves many elderly individuals die as a consequence of dehydration. This is partially due to deficits in mechanisms controlling thirst. Reduced thirst following dipsogenic stimuli is well documented in aged humans and rodents. Low in vivo long-chain omega-3 fatty acid levels, as can occur in aging, have been shown to alter body fluid and sodium homeostasis. Therefore, the effect of dietary omega-3 fatty acid supplementation on drinking responses in aged rats was examined. Omega-3 fatty acids reversed thirst deficits in aged rats following dehydration and hypertonic stimuli; angiotensin (ANG) II induced drinking was unaffected in aged rats. Plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were alt... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580212 Thu, 05 Jan 2012 05:00:00 +0100 5580212 http://www.medworm.com/index.php?rid=5580211&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226488%26dopt%3DAbstract Authors: Qiu G, Spangler EL, Wan R, Miller M, Mattson MP, So KF, Cabo RD, Zou S, Ingram DK Abstract Glucocorticoids (GC)-corticosterone (CORT) in rodents and cortisol in primates-are stress-induced hormones secreted by adrenal glands that interact with the hypothalamic pituitary axis. High levels of cortisol in humans are observed in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), as well as in diabetes, post-traumatic stress syndrome, and major depression. Experimental models of diabetes in rats and mice have demonstrated that reduction of CORT reduces learning and memory deficits and attenuates loss of neuronal viability and plasticity. In contrast to the negative associations of elevated GC levels, CORT is moderately elevated in dieta... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580211 Thu, 05 Jan 2012 05:00:00 +0100 5580211 http://www.medworm.com/index.php?rid=5580210&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226489%26dopt%3DAbstract Authors: Arnaldi D, Campus C, Ferrara M, Famà F, Picco A, De Carli F, Accardo J, Brugnolo A, Sambuceti G, Morbelli S, Nobili F Abstract Subtle cognitive impairment can be detected in early Parkinson's disease (PD). In a consecutive series of de novo, drug-naive PD patients, we applied stepwise regression analysis to assess which clinical, neuropsychological, and functional neuroimaging (dopamine transporter [DAT] and perfusion single photon emission computed tomography [SPECT]) characteristics at baseline was predictive of cognitive decline during an average follow-up time of about 4 years. Decline both in executive (R(2) = 0.54; p = 0.0001) and visuospatial (R(2) = 0.56; p = 0.0001) functions was predicted by the couple of Unified Parkinson's Disease Rating Scale (UPDRS)-III scor... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580210 Thu, 05 Jan 2012 05:00:00 +0100 5580210 http://www.medworm.com/index.php?rid=5580219&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221882%26dopt%3DAbstract Authors: Charlesworth G, Gandhi S, Bras JM, Barker RA, Burn DJ, Chinnery PF, Gentleman SM, Guerreiro R, Hardy J, Holton JL, Lees A, Morrison K, Sheerin UM, Williams N, Morris H, Revesz T, Wood NW Abstract MAPT has been repeatedly linked with Parkinson's disease (PD) in association studies. Although tau deposition may be seen in PD, its relevance to the pathogenesis of the condition remains unclear. The presence of tau-positive inclusions is, however, the defining feature of progressive supranuclear palsy (PSP), which may often be clinically misdiagnosed as idiopathic PD. On a genetic level, variants in MAPT are the strongest risk factor for PSP. These facts raise the question whether the MAPT association in PD results from contamination with unrecognized cases of PSP. Using only ne... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580219 Wed, 04 Jan 2012 05:00:00 +0100 5580219 http://www.medworm.com/index.php?rid=5580218&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221883%26dopt%3DAbstract Authors: Fuso A, Nicolia V, Ricceri L, Cavallaro RA, Isopi E, Mangia F, Fiorenza MT, Scarpa S Abstract Methylation reactions linked to homocysteine in the one-carbon metabolism are increasingly elicited in Alzheimer's disease, although the association of hyperhomocysteinemia and of low B vitamin levels with the disease is still debated. We previously demonstrated that hyperhomocysteinemia and DNA hypomethylation induced by B vitamin deficiency are associated with PSEN1 and BACE1 overexpression and amyloid production. The present study is aimed at assessing S-adenosylmethionine effects in mice kept under a condition of B vitamin deficiency. To this end, TgCRND8 mice and wild-type littermates were assigned to control or B vitamin deficient diet, with or without S-adenosylmethionine s... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580218 Wed, 04 Jan 2012 05:00:00 +0100 5580218 http://www.medworm.com/index.php?rid=5580217&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221884%26dopt%3DAbstract Authors: Dobricic V, Stefanova E, Jankovic M, Gurunlian N, Novakovic I, Hardy J, Kostic V, Guerreiro R Abstract Alzheimer's disease (AD) is the most common form of dementia. To date, more than 200 mutations in three genes have been identified as cause of early-onset autosomal dominant inherited AD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in Serbian patients with positive family history of AD or/and early-onset AD. We performed a genetic screening for mutations in the coding regions of Presenilins 1 and 2 (PSEN1 and PSEN2), as well as exons 16 and 17 of the Amyloid Precursor Protein gene (APP) in a total of 47 patients from Serbia with a clinical diagnosis of familial and/or early-onset AD (mean age at onset of 60.... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5580217 Wed, 04 Jan 2012 05:00:00 +0100 5580217 http://www.medworm.com/index.php?rid=5568620&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217415%26dopt%3DAbstract We report that older (18-month) C57BL/6J mice suffered greater loss of inner retinal function compared with younger adult mice following intraocular pressure (IOP) challenge. To investigate whether age-related vulnerability to IOP challenge can be modified, we subjected 12-month-old mice to dietary restriction (DR) (alternate-day fasting) for 6 months. Compared with age-matched ad libitum fed controls, DR mice showed greater recovery in inner retinal function following IOP challenge. DR was associated with reduced oxidative stress level following injury and improved mitochondrial oxidative phosphorylation enzyme activity compared with ad libitum controls. Taken together, this study provides in vivo evidence that DR improves functional recovery of the retina following injury and points to t... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568620 Mon, 02 Jan 2012 05:00:00 +0100 5568620 http://www.medworm.com/index.php?rid=5568619&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217416%26dopt%3DAbstract Authors: Lee M, Guo JP, Schwab C, McGeer EG, McGeer PL Abstract Complement plays a vital role in both the innate and adaptive immune systems. It recognizes a target, opsonizes it, generates anaphylatoxins, and directly kills cells through the membrane attack complex (MAC). This final function, which assembles C5b-9(n) on viable cell surfaces, can kill host cells through bystander lysis. Here we identify for the first time compounds that can inhibit bystander lysis while not interfering with the other essential functions of complement. We show that aurin tricarboxylic acid (ATA), aurin quadracarboxylic acid (AQA), and aurin hexacarboxylic acid (AHA), block the addition of C9 to C5b-8 so that the MAC cannot form. These molecules inhibit hemolysis of human, rat, and mouse red cells wi... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568619 Mon, 02 Jan 2012 05:00:00 +0100 5568619 http://www.medworm.com/index.php?rid=5568618&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217417%26dopt%3DAbstract Authors: Viticchi G, Falsetti L, Vernieri F, Altamura C, Bartolini M, Luzzi S, Provinciali L, Silvestrini M Abstract Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BH... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568618 Mon, 02 Jan 2012 05:00:00 +0100 5568618 http://www.medworm.com/index.php?rid=5568617&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217418%26dopt%3DAbstract Authors: Pistell PJ, Spangler EL, Kelly-Bell B, Miller MG, de Cabo R, Ingram DK Abstract We have previously reported that a modified Stone T-maze (STM), using escape from water as motivation, was effective in evaluating learning and memory ability in young C57/BL6 mice. Here we report on the effectiveness and sensitivity of the STM in the assessment of age-related learning and memory deficits in mice using either escape from foot shock or water as the motivational manipulations. C57BL/6Nia mice 7-, 12-, 20- and 24-months old received 15 massed trials in the escape from foot shock motivated STM while C57BL/6Nia mice 5-, 12-, and 25-months old were tested in the escape from water STM. Analysis of errors, the main performance variable, revealed similar results in both versions of the ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568617 Mon, 02 Jan 2012 05:00:00 +0100 5568617 http://www.medworm.com/index.php?rid=5568616&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217419%26dopt%3DAbstract Authors: Lee V, Rekhi E, Kam JH, Jeffery G Abstract Vitamin D(3) plays a key role in immune regulation and may protect against the aging process. A focal point for age-related changes is the outer retina of the eye where there is high metabolic demand resulting in a gradual increase in extracellular deposition, inflammation, and cell loss giving rise to visual decline. Here, we demonstrate that vitamin D(3) administration for only 6 weeks in aged mice significantly impacts on this aging process. Treated mice showed significant reductions in retinal inflammation and levels of amyloid beta (Aβ) accumulation, which is a hallmark of aging. They also had significant reductions in retinal macrophage numbers and marked shifts in their morphology. These changes were reflected in a signifi... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568616 Mon, 02 Jan 2012 05:00:00 +0100 5568616 http://www.medworm.com/index.php?rid=5568623&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209255%26dopt%3DAbstract Authors: Griffioen KJ, Wan R, Brown TR, Okun E, Camandola S, Mughal MR, Phillips TM, Mattson MP Abstract Huntington's disease (HD) is associated with profound autonomic dysfunction including dysregulation of cardiovascular control often preceding cognitive or motor symptoms. Brain-derived neurotrophic factor (BDNF) levels are decreased in the brains of HD patients and HD mouse models, and restoring BDNF levels prevents neuronal loss and extends survival in HD mice. We reasoned that heart rate changes in HD may be associated with altered BDNF signaling in cardiovascular control nuclei in the brainstem. Here we show that heart rate is elevated in HD (N171-82Q) mice at presymptomatic and early disease stages, and heart rate responses to restraint stress are attenuated. BDNF levels wer... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568623 Sat, 31 Dec 2011 05:00:00 +0100 5568623 http://www.medworm.com/index.php?rid=5568621&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22212405%26dopt%3DAbstract Authors: Ye X, Tai W, Zhang D Abstract Although there are numerous studies regarding Alzheimer's disease (AD), the cause and progression of AD are still not well understood. The researches in the past decade implicated amyloid-beta (Aβ) overproduction as a causative event in disease pathogenesis, but still failed to clarify the mechanism of pathology from Aβ production to central neural system defects in AD. The present review raises the hypothesis that the onset of AD pathology is closely related with mitochondrial dysfunction induced by Aβ and brain-derived neurotrophic factor (BDNF) axonal transport deficits. It is well-known that axonal transport defect and attenuation of BDNF-neurotrophic tyrosine receptor kinase 2 (TrkB) signal are fatal to neuronal function and survival. ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568621 Sat, 31 Dec 2011 05:00:00 +0100 5568621 http://www.medworm.com/index.php?rid=5568622&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209410%26dopt%3DAbstract Authors: Kemppainen S, Rantamäki T, Jerónimo-Santos A, Lavasseur G, Autio H, Karpova N, Kärkkäinen E, Stavén S, Miranda HV, Outeiro TF, Diógenes MJ, Laroche S, Davis S, Sebastião AM, Castrén E, Tanila H Abstract Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, learning, and memory. Levels of BDNF and its main receptor TrkB (TrkB.TK) have been reported to be decreased while the levels of the truncated TrkB (TrkB.T1) are increased in Alzheimer's disease. We show here that incubation with amyloid-β increased TrkB.T1 receptor levels and decreased TrkB.TK levels in primary neurons. In vivo, APPswe/PS1dE9 transgenic mice (APdE9) showed an age-dependent relative increase in cortical but not hippocampal TrkB.T1 receptor levels compared with ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5568622 Thu, 29 Dec 2011 05:00:00 +0100 5568622 http://www.medworm.com/index.php?rid=5552878&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206845%26dopt%3DAbstract Authors: Villette V, Poindessous-Jazat F, Bellessort B, Roullot E, Peterschmitt Y, Epelbaum J, Stéphan A, Dutar P Abstract In Alzheimer's disease, amyloid beta peptide (Aβ) accumulation is associated with hippocampal network dysfunction. Intrahippocampal injections of Aβ induce aberrant inhibitory septohippocampal (SH) network activity in vivo and impairment of memory processing. In the present study, we observed, after hippocampal Aβ treatment, a selective loss of neurons projecting to the medial septum (MS) and containing calbindin (CB) and/or somatostatin (SOM). Other GABAergic neuronal subpopulations were not altered. Thus, the present study identifies hippocamposeptal neuron populations as specific targets for Aβ deposits. We observed that in Aβ-treated rats but not in c... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5552878 Tue, 27 Dec 2011 05:00:00 +0100 5552878 http://www.medworm.com/index.php?rid=5552877&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206846%26dopt%3DAbstract We report that neuronal overexpression of the endogenous inhibitor of calpains, calpastatin (CAST), in a mouse model of human Alzheimer's disease (AD) β-amyloidosis, the APP23 mouse, reduces β-amyloid (Aβ) pathology and Aβ levels when comparing aged, double transgenic (tg) APP23/CAST with APP23 mice. Concurrent with Aβ plaque deposition, aged APP23/CAST mice show a decrease in the steady-state brain levels of the amyloid precursor protein (APP) and APP C-terminal fragments (CTFs) when compared with APP23 mice. This CAST-dependent decrease in APP metabolite levels was not observed in single tg CAST mice expressing endogenous APP or in younger, Aβ plaque predepositing APP23/CAST mice. We also determined that the CAST-mediated inhibition of calpain activity in the brain is greater in th... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5552877 Tue, 27 Dec 2011 05:00:00 +0100 5552877 http://www.medworm.com/index.php?rid=5552876&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206847%26dopt%3DAbstract The objective of this study was to assess the relationship of dementia with gene and protein expression of a panel of synaptic markers associated with different synaptic functions in young-, middle-, and oldest-old individuals. The protein and messenger RNA (mRNA) levels of 7 synaptic markers (complexin-1, complexin-2, synaptophysin, synaptobrevin, syntaxin, synaptosomal-associated protein 25 (SNAP-25), and septin-5) were compared in the brains of nondemented and demented individuals ranging from 70 to 103 years of age. One hundred eleven brains were selected to have either no significant neuropathology or only AD-associated pathology (neuritic plaques [NPs] and neurofibrillary tangles [NFTs]). The cohort was then stratified into tertiles as young-old (70-81 years old), middle-old (82-88),... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5552876 Tue, 27 Dec 2011 05:00:00 +0100 5552876 http://www.medworm.com/index.php?rid=5552875&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206848%26dopt%3DAbstract Authors: Ponomareva NV, Goltsov AY, Kunijeva SS, Scheglova NS, Malina DD, Mitrofanov AA, Boikova TI, Rogaev EI Abstract The epsilon4 allele of the apolipoprotein E gene (ApoE), as well as aging increase the risk of Alzheimer's and vascular diseases. Electroencephalogram (EEG) reactivity to hyperventilation (HV) depends on hypocapnia-induced cerebral vasoconstriction, which may be impaired in subjects with subclinical cerebrovascular disease. Quantitative EEG at rest and under 3-minute HV was examined in 125 healthy subjects divided into younger (age range 28-50) and older (age range 51-82) cohorts and stratified by ApoE genotype. The younger ApoE-epsilon4 carriers had excessive EEG reactivity to HV characterized by the manifestation of high-voltage delta, theta activity and sharp w... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5552875 Tue, 27 Dec 2011 05:00:00 +0100 5552875 http://www.medworm.com/index.php?rid=5552879&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197104%26dopt%3DAbstract Authors: Maesako M, Uemura K, Kubota M, Kuzuya A, Sasaki K, Asada M, Watanabe K, Hayashida N, Ihara M, Ito H, Shimohama S, Kihara T, Kinoshita A Abstract The pathogenesis of Alzheimer's disease (AD) is tightly associated with metabolic dysfunctions. In particular, a potential link between type 2 diabetes (T2DM) and AD has been suggested epidemiologically, clinically, and experimentally, and some studies have suggested that exercise or dietary intervention reduces risk of cognitive decline. However, there is little solid molecular evidence for the effective intervention of metabolic dysfunctions for prevention of AD. In the present study, we established the AD model mice with diabetic conditions through high-fat diet (HFD) to examine the effect of environmental enrichment (EE) on HF... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5552879 Fri, 23 Dec 2011 05:00:00 +0100 5552879 http://www.medworm.com/index.php?rid=5552880&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22196955%26dopt%3DAbstract Authors: Williams KL, Solski JA, Nicholson GA, Blair IP Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the motor cortex, brain stem and spinal cord. Mutations in the valosin-containing protein gene (VCP) were recently described in ALS families. Some of these families included diagnoses of other clinical features including frontotemporal dementia, Paget's disease, inclusion body myopathy, Parkinsonism and limb weakness. We sought to determine the prevalence of VCP mutations in Australian familial (n = 131) and sporadic (n = 48) ALS cohorts diagnosed with classic ALS. No mutations were identified indicating that VCP mutations are not a common cause of classic ALS among Australian cases with ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5552880 Wed, 21 Dec 2011 05:00:00 +0100 5552880 http://www.medworm.com/index.php?rid=5538669&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192241%26dopt%3DAbstract We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538669 Tue, 20 Dec 2011 05:00:00 +0100 5538669 http://www.medworm.com/index.php?rid=5538668&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192242%26dopt%3DAbstract Authors: Peters A, Kemper T Abstract Like humans, rhesus monkeys show cognitive decline and this review considers what structural age-related changes underlie this decline. Some structural measures do not alter significantly with age. These include brain weight, overall cortical thickness; numbers of cortical neurons; and numbers of astrocytes and microglial cells. Other structural measures change with age, but the change does not correlate with cognitive decline. These changes include nerve fiber loss from some fiber tracts, degeneration, and regeneration of myelin sheaths, and increase in the frequency of oligodendrocytes. Among the structural measures that increase in frequency with age and also correlate with cognitive decline are the increased frequency of degenerating myelin ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538668 Tue, 20 Dec 2011 05:00:00 +0100 5538668 http://www.medworm.com/index.php?rid=5538667&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192243%26dopt%3DAbstract This study measured for the first time cortical amyloid-β (Aβ) levels using [(11)C] Pittsburgh Compound B (PiB) positron emission tomography (PET) in a group of nondemented patients with prior depressive episodes. Twenty-eight elderly patients (mean age 61 years, range 51-75, 18 women) with onset of first depressive episode more than 6 years ago but now remitted from depression and 18 healthy subjects (mean age 61 years, range 50-76, 12 women) were included. All subjects were investigated with cognitive testing, 3T magnetic resonance imaging (MRI) and [(11)C]PiB high resolution research tomography (HRRT) positron emission tomography scan. There was no between-groups difference in [(11)C]PiB binding (p = 0.5) and no associations to number of depressive episodes, cognitive performance, or ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538667 Tue, 20 Dec 2011 05:00:00 +0100 5538667 http://www.medworm.com/index.php?rid=5538672&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188719%26dopt%3DAbstract Authors: Collins O, Dillon S, Finucane C, Lawlor B, Kenny RA Abstract Components of the central autonomic network attract the greatest neurofibrillary degeneration and related cell death during the course of Alzheimer's disease (AD). The insular cortex and brainstem are affected from the early stages of disease. Acetylcholine, the main neurotransmitter of the parasympathetic system may be deficient in mild cognitive impairment (MCI). Hence, autonomic dysfunction may be a novel biomarker of neurodegeneration. Autonomic function was examined in 97 MCI participants and 36 controls using beside cardiovascular reflex tests and heart rate variability. The association between dysautonomia and neuropsychiatric deficits was examined. This observational study was conducted in a clinical sett... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538672 Mon, 19 Dec 2011 05:00:00 +0100 5538672 http://www.medworm.com/index.php?rid=5538671&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188720%26dopt%3DAbstract This study investigated the prevalence of imaging abnormalities suggestive of AD in cognitively normal ApoE ε4 carriers using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM). Forty-five cognitive normal ApoE ε4 allele carriers and 45 noncarriers underwent both FDG positron emission tomography and magnetic resonance imaging (MRI). A total of 90 normal database sets were generated for the individual 45 ε4 carriers and 45 noncarriers. Mean z-scores in the predefined AD-specific regions of interest (ROI) were calculated for each ε4 carrier and noncarrier using the individually defined normal database. The prevalence of AD-like hypometabolism and atrophy in the ε4 carriers was 8.9% and 17.7%, respectively, and did not differ significantly... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538671 Mon, 19 Dec 2011 05:00:00 +0100 5538671 http://www.medworm.com/index.php?rid=5538670&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188721%26dopt%3DAbstract Authors: Desbène C, Malaplate-Armand C, Youssef I, Garcia P, Stenger C, Sauvée M, Fischer N, Rimet D, Koziel V, Escanyé MC, Oster T, Kriem B, Yen FT, Pillot T, Olivier JL Abstract Soluble beta-amyloid (Aβ) oligomers are considered to putatively play a critical role in the early synapse loss and cognitive impairment observed in Alzheimer's disease. We previously demonstrated that Aβ oligomers activate cytosolic phospholipase A(2) (cPLA(2)), which specifically releases arachidonic acid from membrane phospholipids. We here observed that cPLA(2) gene inactivation prevented the alterations of cognitive abilities and the reduction of hippocampal synaptic markers levels noticed upon a single intracerebroventricular injection of Aβ oligomers in wild type mice. We further demonstrated... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538670 Mon, 19 Dec 2011 05:00:00 +0100 5538670 http://www.medworm.com/index.php?rid=5538674&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177720%26dopt%3DAbstract Authors: García-Mesa Y, Giménez-Llort L, López LC, Venegas C, Cristòfol R, Escames G, Acuña-Castroviejo D, Sanfeliu C Abstract Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therapeutic value against AD. We assayed physical exercise and melatonin in 3xTg-AD male mice aged from 6 to 12 months, therefore from moderate to advanced phases of AD pathology. Analysis of behavior and brain tissue at termination showed differential patterns of neuroprotection for the 2 treatments. Both treatments decreased soluble amyloid β... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538674 Fri, 16 Dec 2011 05:00:00 +0100 5538674 http://www.medworm.com/index.php?rid=5538673&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177721%26dopt%3DAbstract Authors: Diaz-Corrales FJ, Miyazaki I, Asanuma M, Ruano D, Rios RM Abstract Lewy bodies containing the centrosomal protein γ-tubulin and fragmentation of Golgi apparatus (GA) have been described in nigral neurons of Parkinson's disease (PD) patients. However, the relevance of these features in PD pathophysiology remains unknown. We analyzed the impact of proteasome inhibition in the formation of γ-tubulin-containing aggregates as well as on GA structure. SH-SY5Y cells were treated with the proteasome inhibitor Z-Leu-Leu-Leu-al (MG132) to induce centrosomal-protein aggregates. Then, microtubules (MTs) and Golgi dynamics, as well as the vesicular transport of dopamine transporter (DAT) were evaluated both in vitro and in living cells. MG132 treatment induced γ-tubulin aggregates w... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538673 Fri, 16 Dec 2011 05:00:00 +0100 5538673 http://www.medworm.com/index.php?rid=5538675&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177217%26dopt%3DAbstract Authors: Fling BW, Kwak Y, Peltier SJ, Seidler RD Abstract Numerous studies have identified age differences in brain structure and function that correlate with declines in motor performance. While these investigations have typically focused on activity in isolated regions of the brain, resting state functional connectivity magnetic resonance imaging (MRI) and diffusion tensor imaging allow for more integrative assessments of spatially disparate neural networks. The novel contribution of the current study is to combine both resting state functional connectivity and diffusion tensor imaging to examine motor corticocortical circuits in young and older adults. We find that relatively greater functional connectivity between the primary motor cortices was strongly associated with decreas... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538675 Wed, 14 Dec 2011 05:00:00 +0100 5538675 http://www.medworm.com/index.php?rid=5538682&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169199%26dopt%3DAbstract Authors: Gibson GE, Chen HL, Xu H, Qiu L, Xu Z, Denton TT, Shi Q Abstract Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K(+) depolarization that occurs in cells from AD patients an... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538682 Mon, 12 Dec 2011 05:00:00 +0100 5538682 http://www.medworm.com/index.php?rid=5538681&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169200%26dopt%3DAbstract Authors: Viola AU, Chellappa SL, Archer SN, Pugin F, Götz T, Dijk DJ, Cajochen C Abstract Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538681 Mon, 12 Dec 2011 05:00:00 +0100 5538681 http://www.medworm.com/index.php?rid=5538680&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169201%26dopt%3DAbstract Authors: Chiba S, Takada E, Tadokoro M, Taniguchi T, Kadoyama K, Takenokuchi M, Kato S, Suzuki N Abstract Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a family of inherited dementias caused by tauopathy. A mutation in exon 10 of the tau gene, N279K, causes a particular kindred of FTDP-17, which is predominant for parkinsonism. The disease initially presents as L-dopa resistant parkinsonism which then rapidly progresses. The final pathological features reveal disappearing dopamine (DA) neurons, but the causes remain poorly understood. We previously established a transgenic mouse with human N279K mutant tau as a model for FTDP-17, which showed cognitive dysfunctions caused by the mutant. Here we analyze L-dopa resistant parkinsonism by several behavio... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538680 Mon, 12 Dec 2011 05:00:00 +0100 5538680 http://www.medworm.com/index.php?rid=5538679&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169202%26dopt%3DAbstract Authors: McQuail JA, Bañuelos C, Lasarge CL, Nicolle MM, Bizon JL Abstract Gamma aminobutyric acid (GABA)(B) receptors (GABA(B)Rs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABA(B)R expression and signaling. Thus, we investigated GABA(B)R expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABA(B)R1 and GABA(B)R2 proteins were reduced in the prefrontal cortex of aged rats but these reductions were not associated with s... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538679 Mon, 12 Dec 2011 05:00:00 +0100 5538679 http://www.medworm.com/index.php?rid=5538678&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169203%26dopt%3DAbstract Authors: Krüger U, Wang Y, Kumar S, Mandelkow EM Abstract Modulating the tau level may represent a therapeutic target for Alzheimer's disease (AD), as accumulating evidence shows that Abeta-induced neurodegeneration is mediated by tau. It is therefore important to understand the expression and degradation of tau in neurons. Recently we showed that overexpressed mutant tau and tau aggregates are degraded via the autophagic pathway in an N2a cell model. Here we investigated whether autophagy is involved in the degradation of endogenous tau in cultured primary neurons. We activated this pathway in primary neurons with trehalose, an enhancer of autophagy. This resulted in the reduction of endogenous tau protein. Tau phosphorylation at several sites elevated in AD pathology had little ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538678 Mon, 12 Dec 2011 05:00:00 +0100 5538678 http://www.medworm.com/index.php?rid=5538677&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169204%26dopt%3DAbstract Authors: Carmichael O, Xie J, Fletcher E, Singh B, Decarli C, Abstract Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed l... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538677 Mon, 12 Dec 2011 05:00:00 +0100 5538677 http://www.medworm.com/index.php?rid=5538684&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154820%26dopt%3DAbstract Authors: Park N, Cheon S, Son GH, Cho S, Kim K Abstract Chronic circadian disturbance, a condition of desynchronization between endogenous clock and environmental light-dark (LD) cycle, is known to cause adverse physiological changes including mortality. However, it is yet unclear whether these consequences result from disturbance of endogenous clock or condition of the LD cycle per se. To address this issue, we imposed 3 different periods of LD cycle (T) on wild type and functional clock-defective (Per1(-/-)Per2(-/-)) mice. We found that the disturbed rhythms of locomotor activity and body temperature resulted from interaction of endogenous clock and T cycle and the chronic state of the disturbance suppressed the endogenous circadian rhythm. Interestingly, the endogenous clock and... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538684 Sat, 10 Dec 2011 05:00:00 +0100 5538684 http://www.medworm.com/index.php?rid=5538685&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154819%26dopt%3DAbstract Authors: Lewis DK, Thomas KT, Selvamani A, Sohrabji F Abstract In middle-aged female rats, focal ischemia leads to a larger cortical infarction as compared with younger females. To determine if stroke-induced cytotoxicity in middle-aged females was associated with impaired astrocyte function, astrocytes were harvested and cultured from the ischemic cortex of young and middle-aged female rats. Middle-aged astrocytes cleared significantly less glutamate from media as compared with young female astrocytes. Furthermore, astrocyte-conditioned media from middle-aged female astrocytes induced greater migration of peripheral blood monocyte cells (PBMCs) and expressed higher levels of the chemoattractant macrophage inflammatory protein-1 (MIP-1). Middle-aged astrocytes also induced greater ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538685 Fri, 09 Dec 2011 05:00:00 +0100 5538685 http://www.medworm.com/index.php?rid=5538683&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154821%26dopt%3DAbstract We report here the description of a nonconsanguineous family with 2 affected individuals with a recessively inherited juvenile motor neuron disease. Exome sequencing of these 2 affected individuals led us to identify 2 compound heterozygous deletions leading to a frameshift and a premature stop codon in the SPG11 gene. One of these deletions, c.5199delA in exon 30, has not been previously reported. Interestingly, these deletions are associated with an intrafamilial phenotypic heterogeneity as one affected has atypical juvenile amyotrophic lateral sclerosis (ALS) and the other has classical hereditary spastic paraplegia with thin corpus callosum. Our findings confirm SPG11 as a genetic cause of juvenile amyotrophic lateral sclerosis and indicate that SPG11 mutations could be associated with... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538683 Fri, 09 Dec 2011 05:00:00 +0100 5538683 http://www.medworm.com/index.php?rid=5538676&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169395%26dopt%3DAbstract Authors: Millecamps S, Corcia P, Cazeneuve C, Boillée S, Seilhean D, Danel-Brunaud V, Vandenberghe N, Pradat PF, Le Forestier N, Lacomblez L, Bruneteau G, Camu W, Brice A, Meininger V, Leguern E, Salachas F Abstract Mutations in UBQLN2 encoding ubiquilin-2 have recently been identified in families with dominant X-linked juvenile and adult-onset amyotrophic lateral sclerosis (ALS) and ALS/dementia. Ubiquilin-2 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients. All the previously reported UBQLN2 mutations were localized in 1 of the 12 PXX domains of ubiquilin-2 protein. We sequenced UBQLN2 in 130 French patients with familial ALS (FALS) and absence of male-to-male transmission and the PXX domain in 240 more patients with sporadic ALS (SALS).... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538676 Thu, 08 Dec 2011 05:00:00 +0100 5538676 http://www.medworm.com/index.php?rid=5538687&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154190%26dopt%3DAbstract Authors: Sha SH, Kanicki A, Halsey K, Wearne KA, Schacht J Abstract Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study, 10-month-old female CBA/J mice were placed on either a control or antioxidant-enriched diet and monitored through 24 months of age. Supplementation with vitamins A, C, and E, L-carnitine, and α-lipoic acid significantly increased the antioxidant capacity of inner ear tissues. However, by 24 months of age, the magnitude of hearing loss was equal between the two groups. Likewise, there were no signific... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538687 Tue, 06 Dec 2011 05:00:00 +0100 5538687 http://www.medworm.com/index.php?rid=5538686&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154191%26dopt%3DAbstract Authors: Sheerin UM, Charlesworth G, Bras J, Guerreiro R, Bhatia K, Foltynie T, Limousin P, Silveira-Moriyama L, Lees A, Wood N Abstract Recently 2 groups have independently identified a mutation in the gene 'vacuolar protein sorting 35 homolog' (VPS35 c.1858G>A; p.Asp620Asn) as a possible cause of autosomal dominant Parkinson's disease (PD). In order to assess the frequency of the reported mutation and to search for other possible disease-causing variants in this gene, we sequenced all 17 exons of VPS35 in 96 familial PD cases, and exon 15 (in which the reported mutation is found) in an additional 64 familial PD cases, 175 young-onset PD cases, and 262 sporadic, neuropathologically confirmed PD cases. We identified 1 individual with the p.Asp620Asn mutation and an autosomal dom... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538686 Tue, 06 Dec 2011 05:00:00 +0100 5538686 http://www.medworm.com/index.php?rid=5594992&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004568%2Fabstract%3Frss%3Dyes Abstract: Mutations in valosin-containing protein (VCP) gene, already known to be associated with the multisystemic disorder, inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD), have been recently found also in familial cases of amyotrophic lateral sclerosis (ALS). To further define the frequency of VCP mutations in ALS Italian population, we screened a cohort of 166 familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified a previously reported synonymous mutation (c.2093A>C; p.Q568Q), 2 intronic variants (c.1749-14C>T; c.2085-3C>T), and 1 nucleotide change (c.2814G>T) in the 3′ untranslated region (UTR). Bioinformatical analyses predicted no changes in splicing process or microRNA binding sites. Our results do not confirm a main co... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5594992 Mon, 05 Dec 2011 05:00:00 +0100 5594992 http://www.medworm.com/index.php?rid=5538688&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22153900%26dopt%3DAbstract Authors: Guerreiro RJ, Lohmann E, Kinsella E, Brás JM, Luu N, Gurunlian N, Dursun B, Bilgic B, Santana I, Hanagasi H, Gurvit H, Gibbs JR, Oliveira C, Emre M, Singleton A Abstract Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain disease-causing mutations are thought to exist. We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), prev... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538688 Mon, 05 Dec 2011 05:00:00 +0100 5538688 http://www.medworm.com/index.php?rid=5466736&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004714%2Fabstract%3Frss%3Dyes (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5466736 Sat, 03 Dec 2011 01:16:16 +0100 5466736 http://www.medworm.com/index.php?rid=5466679&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004660%2Fabstract%3Frss%3Dyes (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5466679 Sat, 03 Dec 2011 01:16:16 +0100 5466679 http://www.medworm.com/index.php?rid=5538696&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137929%26dopt%3DAbstract Authors: Tiloca C, Ratti A, Pensato V, Castucci A, Sorarù G, Del Bo R, Corrado L, Cereda C, D'Ascenzo C, Comi GP, Mazzini L, Castellotti B, Ticozzi N, Gellera C, Silani V, Abstract Mutations in valosin-containing protein (VCP) gene, already known to be associated with the multisystemic disorder, inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD), have been recently found also in familial cases of amyotrophic lateral sclerosis (ALS). To further define the frequency of VCP mutations in ALS Italian population, we screened a cohort of 166 familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified a previously reported synonymous mutation (c.2093A>C; p.Q568Q), 2 intronic variants (c.1749-14C>T; c.2085-3C>T), and 1 nucleotid... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538696 Thu, 01 Dec 2011 05:00:00 +0100 5538696 http://www.medworm.com/index.php?rid=5538695&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078168%26dopt%3DAbstract Authors: Morris JC, Selkoe DJ PMID: 22078168 [PubMed - in process] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538695 Thu, 01 Dec 2011 05:00:00 +0100 5538695 http://www.medworm.com/index.php?rid=5538694&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078169%26dopt%3DAbstract Authors: Mayeux R, Schupf N Abstract Identifying a biomarker for Alzheimer's disease that can be obtained from a blood sample has been a goal of researchers for many years. Over the past few years a number of investigators have studied several plasma biomarkers but most frequently plasma amyloid beta (Aβ)40 and Aβ42 while others have explored the use of genetic variants as biomarkers for diagnosis or risk. This review considers the cross-sectional and longitudinal data regarding plasma Aβ40 and Aβ42 as diagnostic biomarkers as well as risk biomarkers. Review of recent genome-wide association studies indicates as many as 10 genetic variants have been associated with susceptibility to Alzheimer's disease (AD). Further analysis suggests that these factors have modest effects on ri... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538694 Thu, 01 Dec 2011 05:00:00 +0100 5538694 http://www.medworm.com/index.php?rid=5538693&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078170%26dopt%3DAbstract Authors: Klunk WE Abstract Since the introduction of amyloid imaging nearly 10 years ago, this technique has gained widespread use and acceptance. More recently, published reports have begun to appear in which amyloid imaging is used to detect the effects of antiamyloid therapies. This review will consider the issues involved in the use of amyloid imaging in the development and evaluation of drugs for the treatment of Alzheimer's disease. Current evidence regarding the postmortem correlates of in vivo amyloid imaging data are considered. The application of amyloid imaging to screening subjects for trials and use as an outcome measure is discussed in light of longitudinal changes in the in vivo amyloid signal. While the bulk of this review is directed at symptomatic patients with de... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538693 Thu, 01 Dec 2011 05:00:00 +0100 5538693 http://www.medworm.com/index.php?rid=5538692&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078171%26dopt%3DAbstract Authors: Sperling R Abstract Functional magnetic resonance imaging (fMRI) is a relative newcomer in the field of biomarkers for Alzheimer's disease (AD). fMRI has several potential advantages, particularly for clinical trials, as it is a noninvasive imaging technique that does not require the injection of contrast agent or radiation exposure and thus can be repeated many times during a longitudinal study. fMRI has relatively high spatial and reasonable temporal resolution, and can be acquired in the same session as structural magnetic resonance imaging. Perhaps most importantly, fMRI may provide useful information about the functional integrity of brain networks supporting memory and other cognitive domains, including the neural correlates of specific behavioral events, such as suc... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538692 Thu, 01 Dec 2011 05:00:00 +0100 5538692 http://www.medworm.com/index.php?rid=5538691&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078172%26dopt%3DAbstract Authors: Holtzman DM Abstract Over the past 15 years, cerebrospinal fluid (CSF) biomarkers have been shown to be useful for both the diagnosis as well as the prognosis in Alzheimer's disease. It has been shown the CSF levels of amyloid-β (Aβ)(42) are a very good marker for the presence of amyloid deposition in the brain regardless of clinical status and that total tau and phosphorylated forms of tau are useful in detection of neurodegeneration. When combined together, these CSF markers are useful not only in differential diagnosis but also in predicting conversion and rate of progression from mild cognitive impairment/very mild dementia to more severe impairment. The markers are also useful in predicting conversion from cognitive normalcy to very mild dementia. This field is brie... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538691 Thu, 01 Dec 2011 05:00:00 +0100 5538691 http://www.medworm.com/index.php?rid=5538690&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078173%26dopt%3DAbstract This article reviews evidence supporting the position that MRI is a biomarker of neurodegenerative atrophy. Topics covered include methods of extracting quantitative and semiquantitative information from structural MRI; imaging-autopsy correlation; and evidence supporting diagnostic and prognostic value of MRI measures. Finally, the place of MRI in a hypothetical model of temporal ordering of AD biomarkers is reviewed. PMID: 22078173 [PubMed - in process] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538690 Thu, 01 Dec 2011 05:00:00 +0100 5538690 http://www.medworm.com/index.php?rid=5538689&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078174%26dopt%3DAbstract Authors: Albert MS Abstract The clinical hallmark of Alzheimer's disease (AD) is a gradual decline in cognitive function. For the majority of patients the initial symptom is an impairment in episodic memory, i.e., the ability to learn and retain new information. This is followed by impairments in other cognitive domains (e.g., executive function, language, spatial ability). This impairment in episodic memory is evident among individuals with mild cognitive impairment (MCI) and can be used to predict likelihood of progression to dementia, particularly in association with AD biomarkers. Additionally, cognitively normal individuals who are likely to progress to mild impairment tend to perform more poorly on tests of episodic memory than do those who remain stable. This cognitive prese... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538689 Thu, 01 Dec 2011 05:00:00 +0100 5538689 http://www.medworm.com/index.php?rid=5538697&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137330%26dopt%3DAbstract Authors: Sanchez-Juan P, Bishop MT, Aulchenko YS, Brandel JP, Rivadeneira F, Struchalin M, Lambert JC, Amouyel P, Combarros O, Sainz J, Carracedo A, Uitterlinden AG, Hofman A, Zerr I, Kretzschmar HA, Laplanche JL, Knight RS, Will RG, van Duijn CM Abstract The aim of our study was to discover genomic variations related to variant Creutzfeldt-Jakob disease (vCJD) susceptibility. A genome-wide association analysis with most vCJD samples available in the world was performed. A series of 93 vCJD UK patients and 1504 UK controls were included in the discovery stage. Our best findings were replicated in an independent population of 22 UK and 20 French vCJD cases. Post hoc analysis to assess our main results included 5711 French controls, 445 Dutch controls, and 446 sporadic Creutzfeldt-Ja... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538697 Wed, 30 Nov 2011 05:00:00 +0100 5538697 http://www.medworm.com/index.php?rid=5538702&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22133276%26dopt%3DAbstract Authors: Kitamura A, Fujita Y, Oishi N, Kalaria RN, Washida K, Maki T, Okamoto Y, Hase Y, Yamada M, Takahashi J, Ito H, Tomimoto H, Fukuyama H, Takahashi R, Ihara M Abstract Rats subjected to bilateral common carotid artery (CCA) occlusion or 2-vessel occlusion (2VO) have been used as animal models of subcortical ischemic vascular dementia. However, this model possesses an inherent limitation in that cerebral blood flow (CBF) drops too sharply and substantially after ligation of CCAs. To circumvent such hypoxic-ischemic conditions, we tested implantation of the ameroid constrictor device on bilateral CCAs of male Wistar-Kyoto rats and more precisely replicated chronic cerebral hypoperfusion by gradual narrowing of the CCAs (2-vessel gradual occlusion; 2VGO). The acute cerebral bloo... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538702 Tue, 29 Nov 2011 05:00:00 +0100 5538702 http://www.medworm.com/index.php?rid=5538701&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22133277%26dopt%3DAbstract We report here that pitavastatin reduces total and phosphorylated tau levels in a cellular model of tauopathy, and in primary neuronal cultures. The decrease caused by pitavastatin is reversed by the addition of mevalonate, or geranylgeranyl pyrophosphate. The maturation of small G proteins, including RhoA was disrupted by pitavastatin, as was the activity of glycogen synthase kinase 3β (GSK3β), a major tau kinase. Toxin A, inhibitor of glycosylation of small G proteins, and Rho kinase (ROCK) inhibitor decreased phosphorylated tau levels. Rho kinase inhibitor also inactivated glycogen synthase kinase 3β. Although the mechanisms responsible for the reduction in tau protein by pitavastatin require further examination, this report sheds light on possible therapeutic approaches to tauopathy... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538701 Tue, 29 Nov 2011 05:00:00 +0100 5538701 http://www.medworm.com/index.php?rid=5538700&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22133278%26dopt%3DAbstract Authors: Dhawan G, Floden AM, Combs CK Abstract Alzheimer's disease (AD) has been well characterized by the presence of reactive microglia, often associated with β-amyloid (Aβ) plaque deposition. The oligomeric form of Aβ peptide (Aβ(o)) has neurotoxic effects in the presence of microglia and is suggested to potentiate proinflammatory changes in microglia in AD. Primary murine microglia cultures stimulated with Aβ(o) displayed increased protein phosphotyrosine and secreted tumor necrosis factor (TNF)-α levels which were attenuated by the Src/Abl inhibitor, dasatinib. Intracerebroventricular infusions of Aβ(o) into C57BL6/J mice stimulated increased microgliosis and protein phosphotyrosine levels that were also attenuated by dasatinib administration. The rodent findings were ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538700 Tue, 29 Nov 2011 05:00:00 +0100 5538700 http://www.medworm.com/index.php?rid=5538699&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22133279%26dopt%3DAbstract Authors: Hwang JH, Chen JC, Hsu CJ, Yang WS, Liu TC Abstract To investigate the relationship between plasma reactive oxygen species (ROS) levels and severity of age-related hearing impairment in humans. We recruited 302 adult subjects aged 40-77 years with normal or symmetrical sensorineural hearing loss. The association of plasma ROS levels on pure tone average of low frequencies (PTA-low) and pure tone average of high frequencies (PTA-high) were analyzed. Luminol-dependent chemiluminescence signals, which reflect hydrogen peroxide (H(2)O(2)), hypochlorite (HOCl/OCl(-)) and hydroxyl radicals (•OH) levels, showed significant positive association with PTA-low and PTA-high after adjusting for age, gender, central obesity, systemic diseases, and health-related habits (smoking, drink... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538699 Tue, 29 Nov 2011 05:00:00 +0100 5538699 http://www.medworm.com/index.php?rid=5538698&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22133280%26dopt%3DAbstract Authors: Roubaud-Baudron C, Krolak-Salmon P, Quadrio I, Mégraud F, Salles N Abstract Recent case-control studies reported an association between H. pylori infection and Alzheimer's disease (AD). Our aim was to compare cognitive impairment, neuroinflammation, and cerebrovascular lesion load in a group of AD patients according to their H. pylori status. For the 53 AD patients included, we assessed: clinical data (vascular comorbidities and cognitive assessment), biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4 genotype; cerebrospinal fluid [CSF] total tau protein [Tau], phospho-tau(181) protein [pTau(181)]), and amyloid beta peptide levels, serum/CSF-cytokines (interleukin [IL]-1β, IL-6, IL-8, tumor necrosis factor [TNF]-α) and pepsinogen I/pepsinogen... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538698 Tue, 29 Nov 2011 05:00:00 +0100 5538698 http://www.medworm.com/index.php?rid=5594993&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS019745801100460X%2Fabstract%3Frss%3Dyes We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5594993 Mon, 28 Nov 2011 05:00:00 +0100 5594993 http://www.medworm.com/index.php?rid=5594991&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004301%2Fabstract%3Frss%3Dyes Abstract: Based on the substantial overlap in clinical and pathological characteristics of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) with Alzheimer disease (AD) and Parkinson disease (PD) we hypothesized that these disorders might share underlying genetic factors. The contribution of both sequence and copy number variants (CNVs) in known AD and PD genes to the genetic etiology of DLB and PDD however is currently unclear. Therefore, we performed a gene-based mutation analysis of all major AD and PD genes in 99 DLB and 75 PDD patients, including familial and sporadic forms, from Flanders, Belgium. Also, copy number variants in APP, SNCA, and PARK2 were determined. In the AD genes we detected proven pathogenic missense mutations in PSEN1 and PSEN2, and 2 novel... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5594991 Mon, 28 Nov 2011 05:00:00 +0100 5594991 http://www.medworm.com/index.php?rid=5538704&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22130206%26dopt%3DAbstract This study suggests that both DLB and DAT patients show abnormal temporal dynamics of visual selective attention, presumably due to a greater intertarget competition for limited processing capacity. More generally, these findings reinforce the notion that deficits of attentional control processes are more severe in DLB patients as compared with DAT patients. PMID: 22130206 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538704 Mon, 28 Nov 2011 05:00:00 +0100 5538704 http://www.medworm.com/index.php?rid=5538703&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22130207%26dopt%3DAbstract In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538703 Mon, 28 Nov 2011 05:00:00 +0100 5538703 http://www.medworm.com/index.php?rid=5538705&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118948%26dopt%3DAbstract Authors: Philipson O, Lord A, Lalowski M, Soliymani R, Baumann M, Thyberg J, Bogdanovic N, Olofsson T, Tjernberg LO, Ingelsson M, Lannfelt L, Kalimo H, Nilsson LN Abstract The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538705 Sat, 26 Nov 2011 05:00:00 +0100 5538705 http://www.medworm.com/index.php?rid=5538711&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118942%26dopt%3DAbstract Authors: Shan L, Bossers K, Luchetti S, Balesar R, Lethbridge N, Chazot PL, Bao AM, Swaab DF Abstract Earlier studies showed neuronal histamine production in the hypothalamic tuberomamillary nucleus to be unchanged in Parkinson's disease (PD), whereas the histamine levels and innervation in the substantia nigra (SN) increased. In the present study we used quantitative polymerase chain reaction (qPCR) to assess the changes in the histaminergic system in the SN, caudate nucleus (CN), and putamen (PU) in 7 PD patients and 7 controls. The messenger RNA (mRNA) expression of the histamine receptor-3 (H(3)R), which was localized immunocytochemically in the large pigmented neurons, was significantly decreased in the SN in PD, while histamine receptor-4 (H(4)R)-mRNA expression showed a sign... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538711 Fri, 25 Nov 2011 05:00:00 +0100 5538711 http://www.medworm.com/index.php?rid=5538710&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118943%26dopt%3DAbstract Authors: Meeus B, Verstraeten A, Crosiers D, Engelborghs S, Van den Broeck M, Mattheijssens M, Peeters K, Corsmit E, Elinck E, Pickut B, Vandenberghe R, Cras P, De Deyn PP, Van Broeckhoven C, Theuns J Abstract Based on the substantial overlap in clinical and pathological characteristics of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) with Alzheimer disease (AD) and Parkinson disease (PD) we hypothesized that these disorders might share underlying genetic factors. The contribution of both sequence and copy number variants (CNVs) in known AD and PD genes to the genetic etiology of DLB and PDD however is currently unclear. Therefore, we performed a gene-based mutation analysis of all major AD and PD genes in 99 DLB and 75 PDD patients, including familial a... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538710 Fri, 25 Nov 2011 05:00:00 +0100 5538710 http://www.medworm.com/index.php?rid=5538709&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118944%26dopt%3DAbstract The objective of this study was to examine the differences in oscillatory brain dynamics in Alzheimer's disease (AD) according to age at onset using quantitative electroencephalography (EEG). We examined resting state electroencephalograms of 320 probable AD patients and 246 controls, both categorized into a young (≤ 65 years) and old (> 65 years) group. Relative power in 4 different frequency bands was calculated. The effect of age on global and regional relative power was examined. Globally, young AD patients showed lower alpha- and higher delta-power than old AD patients. Regional analysis showed that these differences were most pronounced in the parieto-occipital region. Young AD patients had lower beta- and higher theta-power than old patients in all but the temporal regions. In ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538709 Fri, 25 Nov 2011 05:00:00 +0100 5538709 http://www.medworm.com/index.php?rid=5538708&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118945%26dopt%3DAbstract Authors: Goos JD, Teunissen CE, Veerhuis R, Verwey NA, Barkhof F, Blankenstein MA, Scheltens P, van der Flier WM Abstract Cerebral microbleeds (MBs) may relate to amyloid in dementia. We selected 26 probable Alzheimer's disease (AD) patients with MBs, 26 age- and sex-matched AD patients without MBs, 11 vascular dementia (VaD) patients, and 22 patients with subjective complaints. We measured amyloid beta 1-42 (Aβ42) and 1-40 (Aβ40) in cerebrospinal fluid (CSF) and plasma, and blood-brain barrier (BBB) function using albumin ratios. CSF Aβ42 was lowest in AD with MBs, whereas Aβ40 was selectively decreased in VaD. In plasma, amyloid-beta was nonsignificantly elevated in VaD compared with controls. Higher albumin ratios in VaD suggested blood-brain barrier dysfunction. A MB patter... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538708 Fri, 25 Nov 2011 05:00:00 +0100 5538708 http://www.medworm.com/index.php?rid=5538707&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118946%26dopt%3DAbstract Authors: Mills JD, Janitz M Abstract Alternative splicing (AS) is a post-transcriptional process that occurs in multiexon genes, and errors in this process have been implicated in many human diseases. Until recently, technological limitations prevented AS from being examined at the genome-wide scale. With the advent of new technologies, including exon arrays and next-generation sequencing (NGS) techniques (e.g., RNA-Seq), a higher resolution view of the human transcriptome is now available. This is particularly applicable in the study of neurodegenerative brain diseases (NBDs), such as Alzheimer's disease and Parkinson's disease, because the brain has the greatest amount of alternative splicing of all human tissues. Although many of the AS events associated with these disorders wer... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538707 Fri, 25 Nov 2011 05:00:00 +0100 5538707 http://www.medworm.com/index.php?rid=5538706&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118947%26dopt%3DAbstract Authors: Hou J, Pakkenberg B Abstract The present study is aimed to assess age-related structural changes in corpus callosum with stereology in 21 postmortem human brains without neuropathology, of age 65-75 (Group A, n = 7), 80-85 (Group B, n = 7), and 94-105 (Group C, n = 7) years. Cross-sectional area, fiber number and density decrease in Group B compared with Group A, then remain unchanged in Group C. Mean fiber diameter increases with age. Cross-sectional area shows strong positive correlation to fiber numbers and negative correlation to mean fiber thickness. With age, modest but significant change in fiber size including a decrease in the percentage of 1-2-μm fibers and an increase in 2-3-μm fibers was observed. Fiber density shows a steeper decline with age in the anterior... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538706 Fri, 25 Nov 2011 05:00:00 +0100 5538706 http://www.medworm.com/index.php?rid=5538717&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118902%26dopt%3DAbstract Authors: Miguel L, Avequin T, Delarue M, Feuillette S, Frébourg T, Campion D, Lecourtois M Abstract Recently, the fused in sarcoma/translated in liposarcoma (FUS) protein has been identified as a major constituent of nuclear and/or cytoplasmic ubiquitin-positive inclusions in patients with frontotemporal lobar degeneration or amyotrophic lateral sclerosis. The molecular mechanisms underlying FUS toxicity are currently not understood. To address aspects of FUS pathogenesis in vivo, we have generated new Drosophila transgenic models expressing a full-length wild-type isoform of human FUS protein. We found that when expressed in retinal cells, FUS proteins are mainly recovered as soluble forms, and their overexpression results in a mild eye phenotype, with malformed interommatidial b... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538717 Wed, 23 Nov 2011 05:00:00 +0100 5538717 http://www.medworm.com/index.php?rid=5538715&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118903%26dopt%3DAbstract Authors: Ono K, Mochizuki H, Ikeda T, Nihira T, Takasaki JI, Teplow DB, Yamada M Abstract α-Synuclein (αS) assembly has been implicated as a critical step in the development of Lewy body diseases such as Parkinson's disease and dementia with Lewy bodies. Melatonin (Mel), a secretory product of the pineal gland, is known to have beneficial effects such as an antioxidant function and neuroprotection. To elucidate whether Mel has an antiassembly effect, here we used circular dichroism spectroscopy, photoinduced crosslinking of unmodified proteins, thioflavin S fluorescence, size exclusion chromatography, electron microscopy and atomic force microscopy to examine the effects of Mel on the αS assembly. We also examined the effects of Mel on αS-induced cytotoxicity by assaying 3-[4,5... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538715 Wed, 23 Nov 2011 05:00:00 +0100 5538715 http://www.medworm.com/index.php?rid=5538712&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118904%26dopt%3DAbstract We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. PMID: 22118904 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5538712 Wed, 23 Nov 2011 05:00:00 +0100 5538712 http://www.medworm.com/index.php?rid=5429313&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004386%2Fabstract%3Frss%3Dyes (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5429313 Mon, 21 Nov 2011 00:10:48 +0100 5429313 http://www.medworm.com/index.php?rid=5429253&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004337%2Fabstract%3Frss%3Dyes (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5429253 Mon, 21 Nov 2011 00:10:48 +0100 5429253 http://www.medworm.com/index.php?rid=5446572&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22104734%26dopt%3DAbstract Authors: Salthouse TA Abstract Although differences among people are frequently assumed to increase with age, cross-sectional comparisons of measures of brain structure and measures of cognitive functioning often reveal similar magnitudes of between-person variability across most of adulthood. The phenomenon of nearly constant variability despite systematically lower means with increased age suggests that individual differences in rates of aging may be relatively small, particularly compared with the individual differences apparent at any age. The current study examined between-person variability in cross-sectional means and in short-term longitudinal changes in 5 cognitive abilities at different ages in adulthood. The variability in both level and change in cognitive performance w... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5446572 Fri, 18 Nov 2011 05:00:00 +0100 5446572 http://www.medworm.com/index.php?rid=5428014&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22088679%26dopt%3DAbstract In conclusion, binding deficits and vulnerability to proactive interference are present in persons with MCI and are associated with different brain markers. However, only binding deficits predict progression to dementia. PMID: 22088679 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428014 Mon, 14 Nov 2011 05:00:00 +0100 5428014 http://www.medworm.com/index.php?rid=5428013&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22088680%26dopt%3DAbstract Authors: Mehan ND, Strauss KI Abstract This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12-16 weeks) and juveniles (5-6 weeks). Motor coordination and certain cognitive deficits showed age-dependence both before and after injury. Brain proteins were analyzed using silver-stained two-dimensional electrophoresis gels. Spot volume changes (>2-fold change, p<0.01) were identified between age and injury groups using comp... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428013 Mon, 14 Nov 2011 05:00:00 +0100 5428013 http://www.medworm.com/index.php?rid=5594990&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011004064%2Fabstract%3Frss%3Dyes Abstract: The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene has been associated with stroke. The majority of the reported ALOX5AP associations have considered non-radiologically confirmed infarcts as the stroke phenotype. We assessed the association of genetic variants in ALOX5AP with stroke defined by the presence of infarcts on brain magnetic resonance imaging (MRI). We studied 202 persons with MRI-defined brain infarcts and 487 healthy individuals of Caribbean Hispanic ancestry. Another sample of European ancestry comprised 1823 persons with MRI-defined brain infarct and 7578 control subjects. Subjects were genotyped for the 4 single nucleotide polymorphisms (SNPs) that define ALOX5AP HapA haplotype. No association was found between SNPs and MRI-defined brain infarcts. ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5594990 Fri, 11 Nov 2011 05:00:00 +0100 5594990 http://www.medworm.com/index.php?rid=5428015&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079157%26dopt%3DAbstract Authors: Poisnel G, Hérard AS, El Tannir El Tayara N, Bourrin E, Volk A, Kober F, Delatour B, Delzescaux T, Debeir T, Rooney T, Benavides J, Hantraye P, Dhenain M Abstract Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428015 Fri, 11 Nov 2011 05:00:00 +0100 5428015 http://www.medworm.com/index.php?rid=5428016&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079058%26dopt%3DAbstract Authors: Sadikov T, Simon AJ, Avraham-Lubin BC, Dratviman-Storobinsky O, Cohen Y, Goldenberg-Cohen N Abstract Mutations in the LMNA gene encoding lamins A/C are responsible for Hutchinson-Gilford syndrome (HGS), a disorder of premature aging. Cataract is 1 of the main manifestations. The most prevalent mutation in Hutchinson-Gilford syndrome is C1824T, which activates a cryptic splice donor site to produce an abnormal lamin A protein. The purpose of this study was to investigate a possible association of the C1824T mutation with age-related cataract. Anterior lens capsule material was collected during cataract extraction surgery from 178 patients with senile cataract during 2007-2008. DNA and mRNA were extracted and sequenced for the LMNA gene. DNA and cDNA were screened for the C1... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428016 Thu, 10 Nov 2011 05:00:00 +0100 5428016 http://www.medworm.com/index.php?rid=5428018&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078485%26dopt%3DAbstract This study investigated the hypothesis that vascular risk factors are amyloidogenic. Participants were 43 persons, most with normal cognition or mild cognitive impairment. Vascular risk was quantified using the Framingham Coronary Risk Profile (FCRP) score. Cerebral amyloid was measured by [(11)C]Pittsburgh compound B (PIB) positron emission tomography (PET) and quantified with a Global PIB index, which is the average of distribution volume ratios in selected cortical regions of interest. In a bivariate model FCRP accounted for 16% of the variance in PIB index (p < 0.008) and the positive association remained significant controlling for age and sex. The effect of FCRP was independent of apolipoprotein E (APOE) genotype, which was also associated as expected with PIB. Carotid intima-medi... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428018 Wed, 09 Nov 2011 05:00:00 +0100 5428018 http://www.medworm.com/index.php?rid=5428017&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078486%26dopt%3DAbstract Authors: Koppers M, van Blitterswijk MM, Vlam L, Rowicka PA, van Vught PW, Groen EJ, Spliet WG, Engelen-Lee J, Schelhaas HJ, de Visser M, van der Kooi AJ, van der Pol WL, Pasterkamp RJ, Veldink JH, van den Berg LH Abstract Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known. To determine the identity and frequency of VCP mutations we screened a cohort of 93 familial ALS, 754 ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428017 Wed, 09 Nov 2011 05:00:00 +0100 5428017 http://www.medworm.com/index.php?rid=5428020&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074806%26dopt%3DAbstract We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in 2 age groups of younger (≤ 45 years) and older (≥ 60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to 2 odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects' absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in perip... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428020 Tue, 08 Nov 2011 05:00:00 +0100 5428020 http://www.medworm.com/index.php?rid=5428019&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074807%26dopt%3DAbstract Authors: Barral S, Fernández-Cadenas I, Bis JC, Montaner J, Ikram AM, Launer LJ, Fornage M, Schmidt H, Brickman AM, Seshadri S, Mayeux R Abstract The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene has been associated with stroke. The majority of the reported ALOX5AP associations have considered non-radiologically confirmed infarcts as the stroke phenotype. We assessed the association of genetic variants in ALOX5AP with stroke defined by the presence of infarcts on brain magnetic resonance imaging (MRI). We studied 202 persons with MRI-defined brain infarcts and 487 healthy individuals of Caribbean Hispanic ancestry. Another sample of European ancestry comprised 1823 persons with MRI-defined brain infarct and 7578 control subjects. Subjects were genotyped for the 4 s... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428019 Tue, 08 Nov 2011 05:00:00 +0100 5428019 http://www.medworm.com/index.php?rid=5428022&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22071123%26dopt%3DAbstract Authors: Ancelin ML, Carrière I, Helmer C, Rouaud O, Pasquier F, Berr C, Chaudieu I, Ritchie K Abstract The aim of this study was to evaluate the effects of anti-inflammatory intake on cognitive function in 7234 community-dwelling elderly persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated at baseline, and 2, 4, and 7 years later. Multivariate logistic regression analyses were adjusted for sociodemographic, behavioral, physical, mental health variables, and genetic vulnerability (apolipoprotein E ε4). Elderly women taking inhaled corticosteroids were at increased risk for cognitive decline over 7 years in executive functioning (odds ratio, 1.76; 95% confidence interval, 1.14-2.71; p = 0.04); the effect being increased after con... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428022 Mon, 07 Nov 2011 05:00:00 +0100 5428022 http://www.medworm.com/index.php?rid=5428021&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22071124%26dopt%3DAbstract We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term poten... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428021 Mon, 07 Nov 2011 05:00:00 +0100 5428021 http://www.medworm.com/index.php?rid=5428024&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056199%26dopt%3DAbstract This study suggests that genetic (APOE ε4) and environmental (education) factors are not only independently but also interactively related to dementia risk and that high education may buffer the negative effect of APOE ε4 on dementia occurrence. PMID: 22056199 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428024 Fri, 04 Nov 2011 04:00:00 +0100 5428024 http://www.medworm.com/index.php?rid=5428023&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056200%26dopt%3DAbstract This study also suggests that modulation of Aβ-induced NF-κB activation could be a potential therapeutic strategy for Alzheimer's disease. PMID: 22056200 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428023 Fri, 04 Nov 2011 04:00:00 +0100 5428023 http://www.medworm.com/index.php?rid=5428028&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054870%26dopt%3DAbstract Authors: De Jager PL, Shulman JM, Chibnik LB, Keenan BT, Raj T, Wilson RS, Yu L, Leurgans SE, Tran D, Aubin C, Anderson CD, Biffi A, Corneveaux JJ, Huentelman MJ, , Rosand J, Daly MJ, Myers AJ, Reiman EM, Bennett DA, Evans DA Abstract Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Because common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subje... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428028 Thu, 03 Nov 2011 04:00:00 +0100 5428028 http://www.medworm.com/index.php?rid=5428027&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054871%26dopt%3DAbstract Authors: Santa-Maria I, Diaz-Ruiz C, Ksiezak-Reding H, Chen A, Ho L, Wang J, Pasinetti GM Abstract Tauopathies are characterized by progressive neurodegeneration caused by intracellular accumulation of hyperphosphorylated tau protein aggregates in the brain. The present study was designed to test whether a grape seed polyphenolic extract (GSPE) previously shown to inhibit tau protein aggregation in vitro could benefit tau-mediated neuropathology and behavior deficits in JNPL3 transgenic mice expressing a human tau protein containing the P301L mutation. Nine-month-old JNPL3 mice were treated with GSPE delivered through their drinking water for 6 months. We found that GSPE treatment significantly reduced the number of motor neurons immunoreactive for hyperphosphorylated and conformat... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428027 Thu, 03 Nov 2011 04:00:00 +0100 5428027 http://www.medworm.com/index.php?rid=5428025&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055719%26dopt%3DAbstract This study underlines the importance of population-based mutation screening of newly identified genes. PMID: 22055719 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428025 Thu, 03 Nov 2011 04:00:00 +0100 5428025 http://www.medworm.com/index.php?rid=5428026&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054872%26dopt%3DAbstract Authors: Ramsøy TZ, Liptrot MG, Skimminge A, Lund TE, Sidaros K, Christensen MS, Baaré W, Paulson OB, Jernigan TL, Siebner HR Abstract Recent research on aging has established important links between the neurobiology of normal aging and age-related decline in episodic memory, yet the exact nature of this relationship is still unknown. Functional neuroimaging of regions such as the medial temporal lobe (MTL) have produced conflicting findings. Using functional magnetic resonance imaging (fMRI), we have recently shown that young healthy individuals show a stronger activation of the MTL during encoding of objects as compared with encoding of positions. Using the same encoding task, the present study addressed the question whether this greater MTL activation during encoding of object... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5428026 Wed, 02 Nov 2011 04:00:00 +0100 5428026 http://www.medworm.com/index.php?rid=5383336&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048123%26dopt%3DAbstract Authors: Diaz-Hernandez JI, Gomez-Villafuertes R, León-Otegui M, Hontecillas-Prieto L, Del Puerto A, Trejo JL, Lucas JJ, Garrido JJ, Gualix J, Miras-Portugal MT, Diaz-Hernandez M Abstract β-amyloid (Aβ) peptide production from amyloid precursor protein (APP) is essential in the formation of the β-amyloid plaques characteristic of Alzheimer's disease. However, the extracellular signals that maintain the balance between nonpathogenic and pathologic forms of APP processing, mediated by α-secretase and β-secretase respectively, remain poorly understood. In the present work, we describe regulation of the processing of APP via the adenosine triphosphate (ATP) receptor P2X7R. In 2 different cellular lines, the inhibition of either native or overexpressed P2X7R increased α-secretase... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383336 Mon, 31 Oct 2011 04:00:00 +0100 5383336 http://www.medworm.com/index.php?rid=5383335&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048124%26dopt%3DAbstract Authors: Marchant NL, Reed BR, Decarli CS, Madison CM, Weiner MW, Chui HC, Jagust WJ Abstract The present study evaluated cerebrovascular disease (CVD), β-amyloid (Aβ), and cognition in clinically normal elderly adults. Fifty-four participants underwent magnetic resonance imaging (MRI), Pittsburgh compound B (PIB)-positron emission tomography (PET) imaging, and neuropsychological evaluation. High white matter hyperintensity burden and/or presence of infarct defined CVD status (CVD-: n = 27; CVD+: n = 27). PIB-positron emission tomography ratios of Aβ deposition were extracted using Logan plotting (cerebellar reference). Presence of high levels of Aβ in prespecified regions determined PIB status (PIB-: n = 33; PIB+: n = 21). Executive functioning and episodic memory were measure... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383335 Mon, 31 Oct 2011 04:00:00 +0100 5383335 http://www.medworm.com/index.php?rid=5383334&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048125%26dopt%3DAbstract In this study, we found that the formation of AVs was mediated by activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the brains of APP/PS1 double transgenic mice, amyloid-beta peptide (Aβ) pathology-bearing model mouse. Injection of sunitinib malate, AMPK inhibitor, to the mice lowered AV formation in their brains. Consistent with our in vivo observations, treatment of SH-SY5Y cells with Aβ enhanced the induction of autophagosomes, which was mediated by Ca(2+)/calmodulin-dependent protein kinase kinase-beta (CaMKKβ)-AMPK signaling, as shown using various inhibitors and small interfering RNA (siRNA). CaMKKβ is a calcium-activated kinase, and the depletion of intracellular calcium by BAPTA-AM, a Ca(2+) chelator, also curtailed Aβ-induced autophagy. Finally, t... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383334 Mon, 31 Oct 2011 04:00:00 +0100 5383334 http://www.medworm.com/index.php?rid=5383337&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036844%26dopt%3DAbstract Authors: Jeong JK, Seo JS, Moon MH, Lee YJ, Seol JW, Park SY Abstract The human prion protein fragment, PrP (106-126), may contain a majority of the pathological features associated with the infectious scrapie isoform of PrP, known as PrP(Sc). Based on our previous findings that hypoxia protects neuronal cells from PrP (106-126)-induced apoptosis and increases cellular prion protein (PrP(C)) expression, we hypothesized that hypoxia-related genes, including hypoxia-inducible factor-1 alpha (HIF-1α), may regulate PrP(C) expression and that these genes may be involved in prion-related neurodegenerative diseases. Hypoxic conditions are known to elicit cellular responses designed to improve cell survival through adaptive processes. Under normoxic conditions, a deferoxamine-mediated ele... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383337 Fri, 28 Oct 2011 04:00:00 +0100 5383337 http://www.medworm.com/index.php?rid=5383343&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035587%26dopt%3DAbstract Authors: Cassano T, Serviddio G, Gaetani S, Romano A, Dipasquale P, Cianci S, Bellanti F, Laconca L, Romano AD, Padalino I, Laferla FM, Nicoletti F, Cuomo V, Vendemiale G Abstract Deficits in glutamate neurotransmission and mitochondrial functions were detected in the frontal cortex (FC) and hippopcampus (HIPP) of aged 3×Tg-Alzheimer's disease (AD) mice, compared with their wild type littermates (non-Tg). In particular, basal levels of glutamate and vesicular glutamate transporter 1 (VGLUT1) expression were reduced in both areas. Cortical glutamate release responded to K(+) stimulation, whereas no peak release was observed in the HIPP of mutant mice. Synaptosomal-associated protein 25 (SNAP-25), glutamate/aspartate transporter (GLAST), glutamate transporter 1 (GLT1) and excitatory... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383343 Thu, 27 Oct 2011 04:00:00 +0100 5383343 http://www.medworm.com/index.php?rid=5383342&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035588%26dopt%3DAbstract This study investigated whether the drug has an inhibitory effect on microglial activation and neuroinflammation, which have been implicated in the progression of neurodegenerative processes. Using cultured microglial cells, it was demonstrated that the drug inhibited inflammatory activation of microglia and a signaling pathway that governs the microglial activation. The drug reduced the expression and production of proinflammatory mediators in bacterial lipopolysaccharide-stimulated microglia cells. The microglia-inhibiting activity of amantadine was also demonstrated in a microglia/neuron coculture and animal models of neuroinflammation and Parkinson's disease. Collectively, our results suggest that amantadine may act on microglia in the central nervous system to inhibit their inflammato... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383342 Thu, 27 Oct 2011 04:00:00 +0100 5383342 http://www.medworm.com/index.php?rid=5383341&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035589%26dopt%3DAbstract Authors: Van Langenhove T, van der Zee J, Engelborghs S, Vandenberghe R, Santens P, Van den Broeck M, Mattheijssens M, Peeters K, Nuytten D, Cras P, De Deyn PP, De Jonghe P, Cruts M, Van Broeckhoven C Abstract There exists considerable clinical and pathological overlap between frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), which implies that these 2 neurodegenerative conditions share common pathogenic mechanisms. Recently, intermediate-length (27-33) polyglutamine (polyQ) expansions in ataxin-2 (ATXN2) have been associated with increased risk for ALS, while expansions of > 34 repeats are known to cause spinocerebellar ataxia type 2 (Sca-2). We identified in 72 ALS patients one patient with a 33 polyQ expansion that was absent in 810 control ind... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383341 Thu, 27 Oct 2011 04:00:00 +0100 5383341 http://www.medworm.com/index.php?rid=5383340&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035590%26dopt%3DAbstract Authors: Bruno MA, Cuello AC Abstract Basal forebrain cholinergic neurons (BFCN), a system involved in learning and memory processes, are highly dependent on a continuous supply of biologically active nerve growth factor (NGF). Age-related cholinergic atrophy and cell loss in normal brains is apparently not complemented by reductions in the levels of NGF as could be expected. In the present work, cortical proNGF/NGF were immunoprecipitated from cortical brain homogenates from young and aged and behaviorally characterized rats and resolved with antinitrotyrosine antibodies to reveal nitration of tyrosine residues in proteins. Cortical proNGF in aged and cognitively impaired rats was found to be a target for peroxynitrite-mediated oxidative damage with correlative impact on decrease ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383340 Thu, 27 Oct 2011 04:00:00 +0100 5383340 http://www.medworm.com/index.php?rid=5383339&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035591%26dopt%3DAbstract Authors: Huynh MB, Villares J, Sepúlveda Díaz JE, Christiaans S, Carpentier G, Ouidja MO, Sissoeff L, Raisman-Vozari R, Papy-Garcia D Abstract Glycosaminoglycans (GAGs) are major extracellular matrix components known to tightly regulate cell behavior by interacting with tissue effectors as trophic factors and other heparin binding proteins. Alterations of GAGs structures might thus modify the nature and extent of these interactions and alter tissue integrity. Here, we studied levels and composition of GAGs isolated from adult and aged human hippocampus and investigated if their changes can influence the function of important trophic factors and the Aβ42 peptide toxicity. Biochemical analyses showed that heparan sulfates are increased in the aged hippocampus. Moreover, GAGs from ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383339 Thu, 27 Oct 2011 04:00:00 +0100 5383339 http://www.medworm.com/index.php?rid=5383338&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035592%26dopt%3DAbstract This study therefore suggests that EE needs to be initiated before the age corresponding to the median lifespan and/or required long duration (> 3 mo) to have an effect on cognitive aging. In addition, we show that EE probably acts through theta-burst-independent mechanisms of synaptic plasticity. PMID: 22035592 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging) Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383338 Thu, 27 Oct 2011 04:00:00 +0100 5383338 http://www.medworm.com/index.php?rid=5429310&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011003538%2Fabstract%3Frss%3Dyes Abstract: In this case-controlled study, we tested susceptible genetic variants for Alzheimer's disease (AD) in CR1, CLU and PICALM from genome-wide association studies (GWAS) in a southern Chinese population. Eight hundred twelve participants consisting of 462 late-onset Alzheimer's disease (LOAD) patients and 350 nondemented control subjects were recruited. We found by multivariate logistic regression analysis, that single nucleotide polymorphisms (SNPs) in CR1 (rs6656401 adjusted allelic p = 0.035; adjusted genotypic p = 0.043) and CLU (rs2279590 adjusted allelic p = 0.035; adjusted genotypic p = 0.006; rs11136000 adjusted allelic p = 0.038; adjusted genotypic p = 0.009) were significantly different between LOAD patients and nondemented controls. For PICALM, LOAD association was found o... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5429310 Thu, 20 Oct 2011 04:00:00 +0100 5429310 http://www.medworm.com/index.php?rid=5383346&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018896%26dopt%3DAbstract Authors: Kantarci K, Lowe VJ, Boeve BF, Weigand SD, Senjem ML, Przybelski SA, Dickson DW, Parisi JE, Knopman DS, Smith GE, Ferman TJ, Petersen RC, Jack CR Abstract Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Our objective was to determine whether the (11)C-Pittsburgh Compound-B (PiB) retention and regional hypometabolism on positron emission tomography (PET) and regional cortical atrophy on magnetic resonance imaging (MRI) are complementary in characterizing patients with DLB and differentiating them from AD. We studied age-, gender-, and education-matched patients with a clinical diagnosis of DLB (n = 21), AD (n = 21), and cognitively normal subjects (n = 42). Hippocampal atrophy, global cortical PiB... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383346 Thu, 20 Oct 2011 04:00:00 +0100 5383346 http://www.medworm.com/index.php?rid=5383345&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019052%26dopt%3DAbstract Authors: Shi M, Furay AR, Sossi V, Aasly JO, Armaly J, Wang Y, Wszolek ZK, Uitti RJ, Hasegawa K, Yokoyama T, Zabetian CP, Leverenz JB, Stoessl AJ, Zhang J Abstract Previous studies demonstrated decreased levels of DJ-1 and α-synuclein (αSYN) in human cerebrospinal fluid (CSF) in patients with Parkinson's disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, corr... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383345 Thu, 20 Oct 2011 04:00:00 +0100 5383345 http://www.medworm.com/index.php?rid=5383344&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019053%26dopt%3DAbstract Authors: Murugesan N, Demarest TG, Madri JA, Pachter JS Abstract Given strong regional specialization of the brain, cerebral angiogenesis may be regionally modified during normal aging. To test this hypothesis, expression of a broad cadre of angiogenesis-associated genes was assayed at the neurovascular unit (NVU) in discrete brain regions of young versus aged mice by laser capture microdissection coupled to quantitative real-time polymerase chain reaction (PCR). Complementary quantitative capillary density/branching studies were performed as well. Effects of physical exercise were also assayed to determine if age-related trends could be reversed. Additionally, gene response to hypoxia was probed to highlight age-associated weaknesses in adapting to this angiogenic stress. Aging im... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383344 Thu, 20 Oct 2011 04:00:00 +0100 5383344 http://www.medworm.com/index.php?rid=5429311&cid=s_36798_168_f&fid=38556&url=http%3A%2F%2Fwww.neurobiologyofaging.org%2Farticle%2FPIIS0197458011003757%2Fabstract%3Frss%3Dyes Abstract: Mutations in the optineurin gene (OPTN) have been reported in rare familial and sporadic amyotrophic lateral sclerosis (ALS) cases. It is yet to be established whether mutations segregate with dominantly inherited familial ALS. We therefore performed mutation analysis in a cohort of 96 autosomal dominant ALS families. A novel heterozygous nonsynonymous variant (c.218C > T, S73L) was identified in one patient; however, analysis in the extended pedigree demonstrated that this variant was inherited from an unaffected parent. The variant was absent in 480 control individuals. The affected serine residue is highly conserved and its substitution is predicted to alter phosphorylation. Despite this, our evidence indicates that this variant is unlikely to play a pathogenic role in the dis... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5429311 Wed, 19 Oct 2011 04:00:00 +0100 5429311 http://www.medworm.com/index.php?rid=5383355&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014619%26dopt%3DAbstract Authors: Miralbell J, Soriano JJ, Spulber G, López-Cancio E, Arenillas JF, Bargalló N, Galán A, Barrios MT, Cáceres C, Alzamora MT, Pera G, Kivipelto M, Wahlund LO, Dávalos A, Mataró M Abstract The aim was to investigate the relationship between blood markers of vascular dysfunction with brain microstructural changes and cognition. Eighty-six participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. We assessed correlations of blood levels of inflammatory biomarkers (C-reactive protein [CRP] and resistin) and fibrinolysis inhibitors (plasminogen activator inhibitor-1 [PAI-1] and A-lipoprotein (Lp (a)) with fractional anisotropy... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383355 Tue, 18 Oct 2011 04:00:00 +0100 5383355 http://www.medworm.com/index.php?rid=5383354&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014620%26dopt%3DAbstract Authors: Pietropaolo S, Delage P, Lebreton F, Crusio WE, Cho YH Abstract Mimicking relevant behavioral features of the human pathology is one of the most important challenges for animal models of neurological disorders including Alzheimer disease (AD). Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages. It is therefore crucial to identify AD-like behavioral alterations which may reliably reflect the early stages of the pathology, thus permitting tests of more efficient early therapeutic interventions. Here, we demonstrated the very early expression of noncognitive AD-like symptoms, i.e., deficits in social intere... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383354 Tue, 18 Oct 2011 04:00:00 +0100 5383354 http://www.medworm.com/index.php?rid=5383353&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015308%26dopt%3DAbstract Authors: Chen LH, Kao PY, Fan YH, Ho DT, Chan CS, Yik PY, Ha JC, Chu LW, Song YQ Abstract In this case-controlled study, we tested susceptible genetic variants for Alzheimer's disease (AD) in CR1, CLU and PICALM from genome-wide association studies (GWAS) in a southern Chinese population. Eight hundred twelve participants consisting of 462 late-onset Alzheimer's disease (LOAD) patients and 350 nondemented control subjects were recruited. We found by multivariate logistic regression analysis, that single nucleotide polymorphisms (SNPs) in CR1 (rs6656401 adjusted allelic p = 0.035; adjusted genotypic p = 0.043) and CLU (rs2279590 adjusted allelic p = 0.035; adjusted genotypic p = 0.006; rs11136000 adjusted allelic p = 0.038; adjusted genotypic p = 0.009) were significantly different ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383353 Mon, 17 Oct 2011 04:00:00 +0100 5383353 http://www.medworm.com/index.php?rid=5383352&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015309%26dopt%3DAbstract Authors: Mansoori N, Tripathi M, Luthra K, Alam R, Lakshmy R, Sharma S, Arulselvi S, Parveen S, Mukhopadhyay AK Abstract Genetic risk factors play an important role in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VaD). In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G/C (rs1800795). CC genotype was associated with elevated levels of plasma homocysteine (p = 0.004) as compared with genotype AA of rs1801131. In AD, we observed a significant (p = 0.04) association with C alleles of rs1801131. Regression analysis re... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383352 Mon, 17 Oct 2011 04:00:00 +0100 5383352 http://www.medworm.com/index.php?rid=5383351&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015310%26dopt%3DAbstract In this study we demonstrate that the expression of nitric oxide (NO) synthase-2 (NOS2), and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) with interferon-γ is higher in microglial-enriched cultures from G93A-SOD1 mice, an ALS animal model, than from wild type mice. The levels of CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor that regulates proinflammatory gene expression, are also upregulated in activated G93A-SOD1 microglial cells. In vivo, systemic lipopolysaccharide also induces an exacerbated neuroinflammatory response in G93A-SOD1 mice versus wild type mice, with increased expression of glial fibrillary acidic protein (GFAP), CD11b, nitric oxide synthase-2, cyclooxygenase-2, proinflammatory cytokines, and C/EBPβ. Finally, we report that C/EBPβ is ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383351 Mon, 17 Oct 2011 04:00:00 +0100 5383351 http://www.medworm.com/index.php?rid=5383350&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015311%26dopt%3DAbstract Authors: Solski JA, Williams KL, Yang S, Nicholson GA, Blair IP Abstract Mutations in the optineurin gene (OPTN) have been reported in rare familial and sporadic amyotrophic lateral sclerosis (ALS) cases. It is yet to be established whether mutations segregate with dominantly inherited familial ALS. We therefore performed mutation analysis in a cohort of 96 autosomal dominant ALS families. A novel heterozygous nonsynonymous variant (c.218C > T, S73L) was identified in one patient; however, analysis in the extended pedigree demonstrated that this variant was inherited from an unaffected parent. The variant was absent in 480 control individuals. The affected serine residue is highly conserved and its substitution is predicted to alter phosphorylation. Despite this, our evidence in... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383350 Mon, 17 Oct 2011 04:00:00 +0100 5383350 http://www.medworm.com/index.php?rid=5383349&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015312%26dopt%3DAbstract Authors: Molina DP, Ariwodola OJ, Linville C, Sonntag WE, Weiner JL, Brunso-Bechtold JK, Adams MM Abstract Alterations in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPA-R) and N-methyl-D-aspartate receptor (NMDA-R) have been documented in aged animals and may contribute to changes in hippocampal-dependent memory. Growth hormone (GH) regulates AMPA-R and NMDA-R-dependent excitatory transmission and decreases with age. Chronic GH treatment mitigates age-related cognitive decline. An in vitro CA1 hippocampal slice preparation was used to compare hippocampal excitatory transmission and plasticity in old animals treated for 6-8 months with either saline or GH. Our findings indicate that GH treatment restores NMDA-R-dependent basal synaptic transmission in old ra... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383349 Mon, 17 Oct 2011 04:00:00 +0100 5383349 http://www.medworm.com/index.php?rid=5383348&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015313%26dopt%3DAbstract Authors: Zhen G, Kim YT, Li RC, Yocum J, Kapoor N, Langer J, Dobrowolski P, Maruyama T, Narumiya S, Doré S Abstract Stroke and Alzheimer's disease (AD) are major age-related neurodegenerative diseases that may worsen the prognosis of each other. Our study was designed to delineate the prostaglandin E(2) EP1 receptor role in AD and in the setting of cerebral ischemia. Genetic deletion of the prostaglandin EP1 receptor significantly attenuated the more severe neuronal damage (38.5 ± 10.6%) and memory loss induced by ischemic insult observed in AD transgenic mice (percentage of viable hippocampal CA1 neurons: 11.2 ± 2.9%) when compared with wild type mice (45.1 ± 9.1%). In addition, we found that the amyloid plaques were reduced in EP1 deleted AD mice. β-amyloid-induced toxicity ... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383348 Mon, 17 Oct 2011 04:00:00 +0100 5383348 http://www.medworm.com/index.php?rid=5383347&cid=s_36798_18_f&fid=36798&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015314%26dopt%3DAbstract Authors: Park CH, Boudrias MH, Rossiter H, Ward NS Abstract Neuroanatomical changes in the aging brain are widely distributed rather than focal. We investigated age-related changes in large-scale functional brain networks by applying graph theory to functional magnetic resonance imaging data acquired during a simple grip task with either dominant or nondominant hand. We measured the effect of age on efficiency of information transfer within a series of hierarchical functional networks composed of the whole brain or component parts of the whole brain. Global efficiency was maintained with aging during dominant hand use, primarily due to increased efficiency in parietal-occipital-cerebellar-related networks. During nondominant hand use, global efficiency, as well as efficiency within... Neurobiology of Aging journals http://www.medworm.com/rss/comments.php?id=5383347 Mon, 17 Oct 2011 04:00:00 +0100 5383347