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 'Acta Neuropathologica' source. Wed, 08 Feb 2012 20:42:54 +0100 http://www.medworm.com/index.php?rid=5668691&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdt6219x63n040538%2F Content Type Journal ArticleCategory CorrespondencePages 1-3DOI 10.1007/s00401-012-0948-xAuthors Rajmohan Murali, Department of Pathology, and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USAThomas Wiesner, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USAMarc K. Rosenblum, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, USABoris C. Bastian, Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5668691 Fri, 03 Feb 2012 17:51:26 +0100 5668691 http://www.medworm.com/index.php?rid=5660873&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk27r626737p4723q%2F Abstract  Development of the cerebellum occurs postnatally and is marked by a rapid proliferation of cerebellar granule neuron precursors (CGNPs). CGNPs are the cells of origin for SHH-driven medulloblastoma, the most common malignant brain tumor in children. Here, we investigated the role of ERK, JNK, and p38 mitogen-activated protein kinases in CGNP proliferation. We found high levels of p38α in proliferating CGNPs. Concomitantly, members of the p38 pathway, such as ASK1, MKK3 and ATF-2, were also elevated. Inhibition of the Shh pathway or CGNP proliferation blunts p38α levels, irrespective of Shh treatment. Strikingly, p38α levels were high in vivo in the external granule layer of the postnatal cerebellum, Shh-dependent mouse medulloblastomas and human medulloblastoma... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5660873 Thu, 02 Feb 2012 18:15:33 +0100 5660873 http://www.medworm.com/index.php?rid=5660874&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft46042r916016564%2F We present the first neuropathological description of a patient with a NIPA1 mutation, and clinical phenotype of complicated HSP with motor neuron disease-like syndrome and cognitive decline. Postmortem examination revealed degeneration of lateral corticospinal tracts and dorsal columns with motor neuron loss. TDP-43 immunostaining showed widespread spinal cord and cerebral skein-like and round neuronal cytoplasmic inclusions. We ruled out NIPA1 mutations in 419 additional cases of motor neuron disease. These findings suggest that hereditary spastic paraplegia due to NIPA1 mutations could represent a TDP-43 proteinopathy. Content Type Journal ArticleCategory Case ReportsPages 1-7DOI 10.1007/s00401-012-0947-yAuthors Maria Martinez-Lage, Department of Pathology and Laboratory Medi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5660874 Thu, 02 Feb 2012 18:15:30 +0100 5660874 http://www.medworm.com/index.php?rid=5660875&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl7181503147wq151%2F Content Type Journal ArticleCategory CorrespondencePages 1-4DOI 10.1007/s00401-012-0945-0Authors Veronica A. Kinsler, Department of Paediatric Dermatology, Great Ormond Street Hospital for Children NHS Trust, London, UKSimon M. L. Paine, Department of Histopathology, Great Ormond Street Hospital for Children NHS Trust, London, UKGlenn W. Anderson, Department of Histopathology, Great Ormond Street Hospital for Children NHS Trust, London, UKD. Saraji Wijesekara, Department of Neurology, Great Ormond Street Hospital for Children NHS Trust, London, UKNeil J. Sebire, Department of Histopathology, Great Ormond Street Hospital for Children NHS Trust, London, UKWui K. Chong, Department of Neuroradiology, Great Ormond Street Hospital for Children NHS Trust, London, UKWilliam Harkness, Departmen... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5660875 Tue, 31 Jan 2012 16:48:19 +0100 5660875 http://www.medworm.com/index.php?rid=5639493&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr737h5km36145645%2F In this study, we examined Aβ pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer’s disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(−)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(−) case, Aβ plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, Aβ plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5639493 Tue, 24 Jan 2012 06:52:02 +0100 5639493 http://www.medworm.com/index.php?rid=5639494&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh174650623t51212%2F Abstract  Matrix metalloproteinases (MMPs) are a family of extracellular proteases involved in the pathogenesis of demyelinating diseases like multiple sclerosis (MS). The aim of the present study was to investigate whether MMPs induce direct myelin degradation, leukocyte infiltration, disruption of the blood–brain barrier (BBB), and/or extracellular matrix remodeling in the pathogenesis of Theiler’s murine encephalomyelitis (TME), a virus-induced model of MS. During the demyelinating phase of TME, the highest transcriptional upregulation was detected for Mmp12, followed by Mmp3. Mmp12 −/− mice showed reduced demyelination, macrophage infiltration, and motor deficits compared with wild-type- and Mmp3 knock-out mice. However, BBB remained unaltered, and the amount of ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5639494 Tue, 24 Jan 2012 06:52:01 +0100 5639494 http://www.medworm.com/index.php?rid=5639495&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F16n23w564q8x6u05%2F Abstract  A fundamental step in pathophysiology of prion diseases is the conversion of the host encoded prion protein (PrPC) into a misfolded isoform (PrPSc) that accumulates mainly in neuronal but also non-neuronal tissues. Prion diseases are transmissible within and between species. In a subset of prion diseases, peripheral prion uptake and subsequent transport to the central nervous system are key to disease initiation. The involvement of retroviruses in this process has been postulated based on the findings that retroviral infections enhance the spread of prion infectivity and PrPSc from cell to cell in vitro. To study whether retroviral infection influences the phenotype of prion disease or the spread of prion infectivity and PrPSc in vivo, we developed a murine model wi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5639495 Tue, 24 Jan 2012 06:51:59 +0100 5639495 http://www.medworm.com/index.php?rid=5611111&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx56617x632142n47%2F Abstract  Saccular intracranial aneurysms (sIA) are pouch-like pathological dilatations of intracranial arteries that develop when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. Some sIAs remain stable over time, but in others mural cells die, the matrix degenerates, and eventually the wall ruptures, causing life-threatening hemorrhage. The wall of unruptured sIAs is characterized by myointimal hyperplasia and organizing thrombus, whereas that of ruptured sIAs is characterized by a decellularized, degenerated matrix and a poorly organized luminal thrombus. Cell-mediated and humoral inflammatory reaction is seen in both, but inflammation is clearly associated with degenerated and ruptured walls. Inflammation, however, seems to be a rea... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5611111 Tue, 17 Jan 2012 07:11:20 +0100 5611111 http://www.medworm.com/index.php?rid=5611114&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F60r78622652k1j14%2F Abstract  Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5611114 Tue, 17 Jan 2012 07:11:19 +0100 5611114 http://www.medworm.com/index.php?rid=5611113&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe7mg64x0201478l0%2F Abstract  Glioblastoma (GBM), the most common malignant brain tumor, is among the most lethal neoplasms, with a median survival of approximately 1 year. Prognosis is poor since GBMs possess a strong migratory and highly invasive potential, making complete surgical resection impossible. Reduced expression of carboxypeptidase E (CPE), a neuropeptide-processing enzyme, in a cell death-resistant glioma cell line and lower CPE expression levels in the cohort of GBM samples of The Cancer Genome Atlas compared to normal brain control specimens prompted us to analyze the function of CPE as a putative tumor suppressor gene. In our samples, CPE was also reduced in GBM compared to normal brain with the strongest loss in cells surrounding hypoxic tumor areas as well as in most gli... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5611113 Tue, 17 Jan 2012 07:11:19 +0100 5611113 http://www.medworm.com/index.php?rid=5611112&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn844026jh7671078%2F In conclusion, our results delineate the mechanisms underlying the deregulation and reveal the functional significance of HMGA1 in controlling MB cell growth and migration/invasion. Importantly, the results highlight the therapeutic potential of targeting HMGA1 in MB patients. Content Type Journal ArticleCategory Original PaperPages 1-19DOI 10.1007/s00401-011-0934-8Authors Kin-Mang Lau, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 38018, 1/F, Clinical Sciences Building, Shatin, New Territories, Hong KongQueeny Kwan Yi Chan, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 38018, 1/F, Clinical Sciences Building, Shatin, New Territories, Hong Ko... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5611112 Tue, 17 Jan 2012 07:11:19 +0100 5611112 http://www.medworm.com/index.php?rid=5573031&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8117564u77k31500%2F Abstract  Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4%) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individu... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5573031 Fri, 06 Jan 2012 16:44:36 +0100 5573031 http://www.medworm.com/index.php?rid=5573032&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy132u08661672288%2F Content Type Journal ArticleCategory CorrespondencePages 1-4DOI 10.1007/s00401-011-0936-6Authors Harald Stefanits, Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097 Vienna, AustriaHerbert Budka, Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097 Vienna, AustriaGabor G. Kovacs, Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097 Vienna, Austria Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5573032 Thu, 05 Jan 2012 17:08:08 +0100 5573032 http://www.medworm.com/index.php?rid=5561986&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F75201h1q22k3u37p%2F Abstract  Brain metastases (BM) are common in cancer patients and are associated with high morbidity and poor prognosis, even after intensive multimodal therapy including resection, radiotherapy (stereotactic radiosurgery or whole brain radiotherapy) and chemotherapy. However, advances in the understanding of the pathobiology of BM and the development of molecular targeted agents hold promise for improved prophylaxis and therapy of BM. Here we provide a comprehensive review of the current concepts on mechanisms of the brain-metastatic cascade involving hematogenous dissemination of tumor cells, attachment to microvessel endothelial cells, extravasation into the brain, interaction with the local microenvironment, angiogenesis and intraparenchymal proliferation. Transendothel... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5561986 Mon, 02 Jan 2012 16:53:26 +0100 5561986 http://www.medworm.com/index.php?rid=5561987&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0p53621q436k7x3%2F Abstract  While cognitive deficits are increasingly recognized as common symptoms in amyotrophic lateral sclerosis (ALS), the underlying histopathologic basis for this is not known, nor has the relevance of neuroinflammatory mechanisms and microglial activation to cognitive impairment (CI) in ALS been systematically analyzed. Staining for neurodegenerative disease pathology, TDP-43, and microglial activation markers (CD68, Iba1) was performed in 102 autopsy cases of ALS, and neuropathology data were related to clinical and neuropsychological measures. ALS with dementia (ALS-D) and ALS with impaired executive function (ALS-Ex) patients showed significant microglial activation in middle frontal and superior or middle temporal (SMT) gyrus regions, as well as significant neuron... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5561987 Sat, 31 Dec 2011 06:37:13 +0100 5561987 http://www.medworm.com/index.php?rid=5561988&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu77770v6m2347k66%2F Abstract  Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, p... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5561988 Fri, 30 Dec 2011 16:42:01 +0100 5561988 http://www.medworm.com/index.php?rid=5526949&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw5222781x653121w%2F Content Type Journal ArticleCategory EditorialPages 1-2DOI 10.1007/s00401-011-0931-yAuthors Stephan Frank, Division of Neuropathology, Institute of Pathology, Schönbeinstrasse 40, 4031 Basel, SwitzerlandMarkus Tolnay, Division of Neuropathology, Institute of Pathology, Schönbeinstrasse 40, 4031 Basel, Switzerland Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5526949 Sat, 17 Dec 2011 16:42:05 +0100 5526949 http://www.medworm.com/index.php?rid=5516338&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F62w34tt713613731%2F Abstract  Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) proteins such as Fis1, Mff, and Mief1. It is also generally accepted that organelle fusion depends on the action of three large GTPases: mitofusins (Mfn1, Mfn2) mediating membrane fusion on the OMM level, and Opa1 which is essential for inner mitochondrial membrane fusion. Significantly, mutations in Drp1, Mfn2, and Opa1 have causally been linked to neurodegenerative conditions. Despite this knowledge, crucial questions such as to how fission of the inner an... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5516338 Fri, 16 Dec 2011 16:57:06 +0100 5516338 http://www.medworm.com/index.php?rid=5516339&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa7w4756nt1773363%2F This study consists of two parts: (1) an observational study using postmortem human brains (n = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm2 in mild, 0.584/cm2 in moderate, and 4.370/cm2 in severe CAA groups with a positive linear correlation (r = 0.6736, p < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs (p = 0.0022). Consistent with the data from human brains, CAA ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5516339 Wed, 14 Dec 2011 16:41:46 +0100 5516339 http://www.medworm.com/index.php?rid=5516340&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb8477m853m3t5180%2F Abstract  Fibrillar αSynuclein is the major constituent of Lewy bodies and Lewy neurites, the protein deposits characteristic for Parkinson’s disease (PD). Multiplications of the αSynuclein gene, as well as point mutations cause familial PD. However, the exact role of αSynuclein in neurodegeneration remains uncertain. Recent research in invertebrates has suggested that oligomeric rather than fibrillizing αSynuclein mediates neurotoxicity. To investigate the impact of αSynuclein aggregation on the progression of neurodegeneration, we expressed variants with different fibrillation propensities in the rat substantia nigra (SN) by means of recombinant adeno-associated viral (AAV) vectors. The formation of proteinase K-resistant αSynuclein aggregates was correlated to th... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5516340 Tue, 13 Dec 2011 17:05:28 +0100 5516340 http://www.medworm.com/index.php?rid=5506732&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F60705x5671203412%2F This study characterizes novel methods to measure individual entorhinal verruca size, and shows that verrucae size correlates to Alzheimer’s pathology. Taken together, these results suggest that verrucae may have the potential to serve as an early and specific morphological marker for mild cognitive impairment and Alzheimer’s disease. Content Type Journal ArticleCategory Original PaperPages 1-12DOI 10.1007/s00401-011-0929-5Authors Jean C. Augustinack, Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149–13th St., Room 2301, Charlestown, MA 02129, USAKristen E. Huber, Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149–13th St., Room ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5506732 Mon, 12 Dec 2011 17:17:04 +0100 5506732 http://www.medworm.com/index.php?rid=5495928&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb7062782837w5361%2F Abstract  Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs) all arise from the Schwann cell lineage. Despite their common origin, these tumor types have distinct pathologies and clinical behaviors; a growing body of evidence indicates that they also arise via distinct pathogenic mechanisms. Identification of the genes that are mutated in genetic diseases characterized by the development of either neurofibromas and MPNSTs [neurofibromatosis type 1 (NF1)] or schwannomas [neurofibromatosis type 2 (NF2), schwannomatosis and Carney complex type 1] has greatly advanced our understanding of these mechanisms. The development of genetically engineered mice with ablation of NF1, NF2, SMARCB1/INI1 or PRKAR1A has confirmed the key role these genes play in ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5495928 Sat, 10 Dec 2011 16:55:02 +0100 5495928 http://www.medworm.com/index.php?rid=5495930&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F28414wh768534166%2F Abstract  The brain tissue obtained from ninety-five cognitively unimpaired subjects, with ages ranging from 22 to 50 years upon death, were immunohistochemically assessed for neurodegenerative changes, i.e., hyperphosphorylated tau (HPτ) and β-amyloid (Aβ) pathology in predilection neuroanatomical areas. HPτ pathology was observed in the transentorhinal cortex and/or the locus coeruleus (LC) in 33% of the subjects, without any obvious risk factors known to alter the microtubule-associated protein. HPτ pathology was noted in the LC in 25 out of 83 subjects (30%), lacking concomitant cortical Aβ or transentorhinal HPτ pathology. This observation was present even when assessing only one routine section of 7 μm thickness. The recent suggestion of prion-like p... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5495930 Sat, 10 Dec 2011 16:55:01 +0100 5495930 http://www.medworm.com/index.php?rid=5495929&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fap1223k043p17k1t%2F Abstract  Camptocormia is a highly disabling syndrome that occurs in various diseases but is particularly associated with Parkinson’s disease (PD). Although first described nearly 200 years ago, the morphological changes associated with camptocormia are still under debate and the pathophysiology is unknown. We analyzed paraspinal muscle biopsies of 14 PD patients with camptocormia and compared the findings to sex-matched postmortem controls of comparable age to exclude biopsy site-specific changes. Camptocormia in PD showed a consistent lesion pattern composed of myopathic changes with type-1 fiber hypertrophy, loss of type-2 fibers, loss of oxidative enzyme activity, and acid phosphatase reactivity of lesions. Ultrastructurally, myofibrillar disorganization and Z-ba... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5495929 Sat, 10 Dec 2011 16:55:01 +0100 5495929 http://www.medworm.com/index.php?rid=5495931&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fuu636721744488w8%2F In conclusion, we demonstrate considerable heterogeneity within MYCN-MB in terms of genetics, tumor biology, and clinical outcome. Thus, assessment of disease group and 10q copy-number status may improve risk stratification of this group and may delineate MYCN-MB with the same dismal prognosis as MYC amplified tumors. Furthermore, based on the enrichment of MYCN and GLI2 amplifications in SHH-driven medulloblastoma, amplification of these downstream signaling intermediates should be taken into account before a patient is enrolled into a clinical trial using a smoothened inhibitor. Content Type Journal ArticleCategory Original PaperPages 1-13DOI 10.1007/s00401-011-0918-8Authors Andrey Korshunov, Department of Neuropathology, University of Heidelberg, Heidelberg, GermanyMarc Remke, ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5495931 Thu, 08 Dec 2011 18:24:19 +0100 5495931 http://www.medworm.com/index.php?rid=5488489&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy22m260577635101%2F Abstract  Maintaining the functional integrity of mitochondria is pivotal for cellular survival. It appears that neuronal homeostasis depends on high-fidelity mitochondria, in particular. Consequently, mitochondrial dysfunction is a fundamental problem associated with a significant number of neurological diseases, including Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and various peripheral neuropathies, as well as the normal aging process. To ensure optimal mitochondrial function, diverse, evolutionarily conserved mitochondrial quality control mechanisms are in place, including the scavenging of toxic reactive oxygen species (ROS) and degradation of damaged mitochondrial proteins, but also turnover... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5488489 Tue, 06 Dec 2011 07:01:37 +0100 5488489 http://www.medworm.com/index.php?rid=5477992&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl527n0148365p400%2F Abstract  The MYC oncogenes are the most commonly amplified loci in medulloblastoma, and have previously been proposed as biomarkers of adverse disease prognosis by us and others. Here, we report focussed and comprehensive investigations of MYCC, MYCN and MYCL in an extensive medulloblastoma cohort (n = 292), aimed to define more precisely their biological significance and optimal clinical application to direct improved disease risk-stratification and individualisation of therapy. MYCC and MYCN expression elevations were multifactorial, associated with high-risk (gene amplification, large-cell/anaplastic pathology (LCA)) and favourable-risk (WNT/SHH molecular subgroups) disease features. Highly variable cellular gene amplification patterns underlay overall MYC copy ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5477992 Fri, 02 Dec 2011 17:30:50 +0100 5477992 http://www.medworm.com/index.php?rid=5477993&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn5644r3713705j18%2F Abstract  The contribution of microRNAs to the initiation, progression, and metastasis of medulloblastoma (MB) remains poorly understood. Metastatic dissemination at diagnosis is present in about 30% of MB patients, and is associated with a dismal prognosis. Using microRNA expression profiling, we demonstrate that the retinal miR-183–96–182 cluster on chromosome 7q32 is highly overexpressed in non-sonic hedgehog MBs (non-SHH-MBs). Expression of miR-182 and miR-183 is associated with cerebellar midline localization, and miR-182 is significantly overexpressed in metastatic MB as compared to non-metastatic tumors. Overexpression of miR-182 in non-SHH-MB increases and knockdown of miR-182 decreases cell migration in vitro. Xenografts overexpressing miR-182 invaded adjacent ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5477993 Thu, 01 Dec 2011 19:29:53 +0100 5477993 http://www.medworm.com/index.php?rid=5477994&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F636123n447361k6p%2F Abstract  Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histological subgrouping (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes. Variations in the number, composition, and nature of the subgroups between studies brought about a consensus conference in... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5477994 Thu, 01 Dec 2011 19:29:51 +0100 5477994 http://www.medworm.com/index.php?rid=5459538&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjqjhm6m210515557%2F Abstract  Focal cortical dysplasias (FCD) which represent a composite group of cortical malformations are increasingly recognized as morphological substrate for severe therapy-refractory epilepsy in children and young adults. However, presurgical evaluation remains challenging as not all FCD variants can be reliably detected by high-resolution magnetic resonance imaging (MRI). Here, we studied a cohort of 52 epilepsy patients with neuropathological evidence for FCD using the 2011 classification of the International League against Epilepsy (ILAE) and systematically analysed those histopathologic features applicable also for MRI diagnostics. Histopathologic parameters included quantitative measurements of cellular profiles, cortical thickness, heterotopic neurons in white mat... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5459538 Sat, 26 Nov 2011 16:48:46 +0100 5459538 http://www.medworm.com/index.php?rid=5450263&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg521130p29881gw8%2F Content Type Journal ArticleCategory ObituaryPages 1-2DOI 10.1007/s00401-011-0917-9Authors Caterina Giannini, Mayo Clinic, Rochester, MN, USA Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5450263 Thu, 24 Nov 2011 17:45:14 +0100 5450263 http://www.medworm.com/index.php?rid=5450264&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl72k00747723h01g%2F Abstract  Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, which also has neuroprotective activity. In view of these dual actions on vessels and neurons, we were interested whether VEGF promotes long distance axonal plasticity in the ischemic brain. Herein, we show that VEGF promotes neurological stroke recovery in mice when delivered in a delayed way starting 3 days after middle cerebral artery occlusion. Using anterograde tract-tracing experiments that we combined with histochemical and molecular biological studies, we demonstrate that although VEGF promoted angiogenesis predominantly in the ischemic hemisphere, pronounced axonal sprouting was induced by VEGF in the contralesional, but not the ipsilesional corticobulbar system. Corticobulbar p... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5450264 Wed, 23 Nov 2011 16:39:24 +0100 5450264 http://www.medworm.com/index.php?rid=5450265&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu1264p5x3717l72g%2F In conclusion, we have generated a global view of the methylation profile of ependymoma. The data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal, but not posterior fossa ependymomas. Hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis. Content Type Journal ArticleCategory Original PaperPages 1-15DOI 10.1007/s00401-011-0904-1Authors Hazel A. Rogers, Children’s Brain Tumour Research Centre, D Floor Medical School, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH UKJohn-Paul Kilday, Children’s Brain Tumour Research Centre, D Floor Medical School, Queen’s ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5450265 Wed, 23 Nov 2011 16:39:22 +0100 5450265 http://www.medworm.com/index.php?rid=5442972&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F338530l0t85t5hn6%2F Abstract  Research into amyotrophic lateral sclerosis (ALS) has been stimulated by a series of genetic and molecular pathology discoveries. The hallmark neuronal cytoplasmic inclusions of sporadic ALS (sALS) predominantly comprise a nuclear RNA processing protein, TDP-43 encoded by the gene TARDBP, a discovery that emerged from high throughput analysis of human brain tissue from patients with frontotemporal dementia (FTD) who share a common molecular pathology with ALS. The link between RNA processing and ALS was further strengthened by the discovery that another genetic locus linking familial ALS (fALS) and FTD was due to mutation of the fused in sarcoma (FUS) gene. Of potentially even greater importance it emerges that TDP-43 accumulation and inclusion formation characteris... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5442972 Mon, 21 Nov 2011 18:09:06 +0100 5442972 http://www.medworm.com/index.php?rid=5442974&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj1138258558410r3%2F We report an autopsy case of rare adult-onset spastic paraplegia type 2 (SPG2) with a novel missense mutation in exon 7 of the proteolipid protein 1 gene (PLP1). The patient was a 67-year-old man whose elder brother had died of a similar disease with onset in his 40s. Thirty-three years before death at the age of 35, he noticed difficulty in walking. He gradually became abasic over a period of 6 years. He also developed progressive dementia and eventually became bed-ridden by 28 years after onset. At autopsy, gross inspection revealed diffuse, moderate atrophy of the cerebrum with a dilated ventricular system and softening of the white matter throughout the central nervous system (CNS). Histopathologically, the CNS showed widespread myelin pallor in the white matter. By cont... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5442974 Sat, 19 Nov 2011 16:51:38 +0100 5442974 http://www.medworm.com/index.php?rid=5442973&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3370885p74700063%2F We present a practical guide for the implementation of recently revised National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an “ABC” score for AD neuropathologic change that incorporates histopathologic assessments of amyloid β deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommenda... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5442973 Sat, 19 Nov 2011 16:51:38 +0100 5442973 http://www.medworm.com/index.php?rid=5442975&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F286t61q75ln4x1u7%2F Content Type Journal ArticleCategory CorrespondencePages 1-4DOI 10.1007/s00401-011-0915-yAuthors Claudia Schwab, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, CanadaSheng Yu, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, CanadaPatrick L. McGeer, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5442975 Sat, 19 Nov 2011 16:51:37 +0100 5442975 http://www.medworm.com/index.php?rid=5442976&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhx77qm1701q5332k%2F Abstract  The deposition of the β-amyloid (Aβ) peptide in senile plaques and cerebral Aβ-amyloid angiopathy can be seeded in β-amyloid precursor protein (APP)-transgenic mice by the intracerebral infusion of brain extracts containing aggregated Aβ. Previous studies of seeded β-amyloid induction have used relatively short incubation periods to dissociate seeded β-amyloid induction from endogenous β-amyloid deposition of the host, thus precluding the analysis of the impact of age and extended incubation periods on the instigation and spread of Aβ lesions in brain. In the present study using R1.40 APP-transgenic mice (which do not develop endogenous Aβ deposition up to 15 months of age) we show that: (1) seeding at 9 months of age does not induce more Aβ d... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5442976 Sat, 19 Nov 2011 16:51:36 +0100 5442976 http://www.medworm.com/index.php?rid=5442977&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa415l065147v61x1%2F Content Type Journal ArticleCategory EditorialPages 1-3DOI 10.1007/s00401-011-0919-7Authors Eileen H. Bigio, Division of Neuropathology, Department of Pathology, Cognitive Neurology and Alzheimer Disease Center, Northwestern Feinberg School of Medicine, 710 N Fairbanks Ct, Olson 2-458, Chicago, IL 60611, USA Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5442977 Sat, 19 Nov 2011 06:52:26 +0100 5442977 http://www.medworm.com/index.php?rid=5432868&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg5304260k43p4321%2F Abstract  The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer’s disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5432868 Fri, 18 Nov 2011 17:28:28 +0100 5432868 http://www.medworm.com/index.php?rid=5432870&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyt5j3j87612242t6%2F Abstract  Mild cognitive impairment (MCI) is rapidly becoming one of the most common clinical manifestations affecting the elderly. The pathologic and molecular substrate of people diagnosed with MCI is not well established. Since MCI is a human specific disorder and neither the clinical nor the neuropathological course appears to follow a direct linear path, it is imperative to characterize neuropathology changes in the brains of people who came to autopsy with a well-characterized clinical diagnosis of MCI. Herein, we discuss findings derived from clinical pathologic studies of autopsy cases who died with a clinical diagnosis of MCI. The heterogeneity of clinical MCI imparts significant challenges to any review of this subject. The pathologic substrate of MCI is equally c... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5432870 Fri, 18 Nov 2011 17:28:27 +0100 5432870 http://www.medworm.com/index.php?rid=5432869&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F017n106343823208%2F Abstract  Neuronal cytoplasmic inclusions (NCIs) containing phosphorylated TDP-43 (p-TDP-43) are the pathological hallmarks of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and FTLD-TDP. The vast majority of NCIs in the brain and spinal cord also label for ubiquitin and p62, however, we have previously reported a subset of TDP-43 proteinopathy patients who have unusual and abundant p62 positive, TDP-43 negative inclusions in the cerebellum and hippocampus. Here we sought to determine whether these cases carry the hexanucleotide repeat expansion in C9orf72. Repeat primer PCR was performed in 36 MND/ALS, FTLD-MND/ALS and FTLD-TDP cases and four controls. Fourteen individuals with the repeat expansion were detected. In all the 14 expansion mutation cases there we... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5432869 Fri, 18 Nov 2011 17:28:27 +0100 5432869 http://www.medworm.com/index.php?rid=5432871&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr4m12114268p1573%2F In this study we have investigated the distribution and the level of expression of kinesin light chains (KLCs) (responsible for binding of cargos during anterograde transport) and of dynein intermediate chain (DIC) (a component of the dynein complex during retrograde transport) in frontal cortex and cerebellar cortex of control subjects and Alzheimer’s disease patients. By immunoblotting, we found a significant decrease in the levels of expression of KLC1 and 2 and DIC in the frontal cortex, but not in the cerebellar cortex, of Alzheimer’s disease patients. A significant decrease in the levels of synaptophysin and of tubulin-β3 proteins, two neuronal markers, was also observed. KLC1 and DIC immunoreactivities did not co-localize with neurofibrillary tangles. The mean mRNA levels... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5432871 Fri, 18 Nov 2011 06:53:47 +0100 5432871 http://www.medworm.com/index.php?rid=5423713&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl13682j87852332r%2F Abstract  The 2011 annual meeting of the Children’s Tumor Foundation, the annual gathering of the neurofibromatosis (NF) research and clinical communities, was attended by 330 participants who discussed integration of new signaling pathways into NF research, the appreciation for NF mutations in sporadic cancers, and an expanding pre-clinical and clinical agenda. NF1, NF2, and schwannomatosis collectively affect approximately 100,000 persons in US, and result from mutations in different genes. Benign tumors of NF1 (neurofibroma and optic pathway glioma) and NF2 (schwannoma, ependymoma, and meningioma) and schwannomatosis (schwannoma) can cause significant morbidity, and there are no proven drug treatments for any form of NF. Each disorder is associated with additional mani... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5423713 Tue, 15 Nov 2011 06:47:18 +0100 5423713 http://www.medworm.com/index.php?rid=5410420&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr6815l27u2624r3p%2F In this study, we examined the neuropathology and clinical features of 20 cases of c9FTD/ALS from a brain bank for neurodegenerative disorders. Included are six patients clinically diagnosed with ALS, eight FTD, one FTD-MND and four Alzheimer-type dementia. Clinical information was unavailable for one patient. Pathologically, the cases all had TDP-43 pathology, but there were three major pathologic groups: ALS, FTLD-MND and FTLD-TDP. The ALS cases were morphologically similar to typical sporadic ALS with almost no extramotor TDP-43 pathology; all had oligodendroglial cytoplasmic inclusions. The FTLD-MND showed predominantly Mackenzie Type 3 TDP-43 pathology, and all had ALS-like pathology in motor neurons, but more extensive extramotor pathology, with oligodendroglial cytoplasmic inc... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5410420 Mon, 14 Nov 2011 16:52:47 +0100 5410420 http://www.medworm.com/index.php?rid=5410421&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg4t56218k5v64443%2F Abstract  Alzheimer’s disease (AD) is multifactorial and, to date, no single cause of the sporadic form of this disease, which accounts for over 99% of the cases, has been established. In AD brain, protein phosphatase-2A (PP2A) activity is known to be compromised due to the cleavage and translocation of its potent endogenous inhibitor, I2PP2A, from the neuronal nucleus to the cytoplasm. Here, we show that adeno-associated virus vector-induced expression of the N-terminal I2NTF and C-terminal I2CTF halves of I2PP2A, also called SET, in brain reproduced key features of AD in Wistar rats. The I2NTF–CTF rats showed a decrease in brain PP2A activity, abnormal hyperphosphorylation and aggregation of tau, a loss of neuronal plasticity and impairment in spatial reference and work... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5410421 Mon, 14 Nov 2011 16:52:46 +0100 5410421 http://www.medworm.com/index.php?rid=5389884&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F458v700477303k30%2F Abstract  Mitochondria are dynamic organelles which are essential for many cellular processes, such as ATP production by oxidative phosphorylation, lipid metabolism, assembly of iron sulfur clusters, regulation of calcium homeostasis, and cell death pathways. The dynamic changes in mitochondrial morphology, connectivity, and subcellular distribution are critically dependent on a highly regulated fusion and fission machinery. Mitochondrial function, dynamics, and quality control are vital for the maintenance of neuronal integrity. Indeed, there is mounting evidence that mitochondrial dysfunction plays a central role in several neurodegenerative diseases. In particular, the identification of genes linked to rare familial variants of Parkinson’s disease has fueled research o... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5389884 Sat, 05 Nov 2011 17:08:03 +0100 5389884 http://www.medworm.com/index.php?rid=5389883&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc5r810n023113x00%2F Content Type Journal ArticleCategory CorrespondencePages 1-4DOI 10.1007/s00401-011-0903-2Authors Adelheid Woehrer, Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18–20, 1097 Vienna, AustriaIrene Slavc, Department of Pediatrics, Medical University of Vienna, Vienna, AustriaAndreas Peyrl, Department of Pediatrics, Medical University of Vienna, Vienna, AustriaThomas Czech, Department of Neurosurgery, Medical University of Vienna, Vienna, AustriaChristian Dorfer, Department of Neurosurgery, Medical University of Vienna, Vienna, AustriaDaniela Prayer, Department of Radiology, Medical University of Vienna, Vienna, AustriaSusanne Stary, Department of Pathology, Medical University of Vienna, Vienna, AustriaBerthold Streubel, Department of Pathology, Medical Universi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5389883 Sat, 05 Nov 2011 17:08:03 +0100 5389883 http://www.medworm.com/index.php?rid=5389885&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk28q17p0226401mw%2F We present an assay based on nanoString technology that is capable of rapidly, reliably, and reproducibly assigning clinical FFPE medulloblastoma samples to their molecular subgroup, and which is highly suited for future medulloblastoma clinical trials. Content Type Journal ArticleCategory Methods PaperPages 1-12DOI 10.1007/s00401-011-0899-7Authors Paul A. Northcott, The Arthur and Sonia Labatt Brain Tumour Research Center, Hospital for Sick Children, Toronto, ON, CanadaDavid J. H. Shih, The Arthur and Sonia Labatt Brain Tumour Research Center, Hospital for Sick Children, Toronto, ON, CanadaMarc Remke, Division Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, GermanyYoon-Jae Cho, Department of Neurology, Children’s Hospital Boston, Boston, MA, USAMarcel Kool... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5389885 Sat, 05 Nov 2011 17:08:02 +0100 5389885 http://www.medworm.com/index.php?rid=5389886&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F38uq54q281720976%2F We describe in detail the histopathology of IRIS in natalizumab-associated PML. PML–IRIS, ongoing PML infection, and MS exacerbation may be impossible to discern clinically alone. MRI may provide some clues for distinguishing different pathologies that can be differentiated histologically. In our individual cases, biopsy helped to clarify diagnoses in natalizumab-associated PML. Content Type Journal ArticleCategory Original PaperPages 1-11DOI 10.1007/s00401-011-0900-5Authors Imke Metz, Department of Neuropathology, University Medical Center, Georg August University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, GermanyErnst-Wilhelm Radue, Medical Image Analysis Center (MIAC), University Hospital Basel, Basel, SwitzerlandAgustin Oterino, Service of Neurology, University Hosp... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5389886 Sat, 05 Nov 2011 17:08:01 +0100 5389886 http://www.medworm.com/index.php?rid=5389887&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fagur145475010236%2F In this report, we examined whether tau nitration at these sites also occurs in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick’s disease (PiD), three neurodegenerative tauopathies that contain abundant tau deposits within glial and neuronal cell types but lack amyloid deposition. The reactivity of these antibodies was also compared to two previously characterized antibodies Tau-nY18 and Tau-nY29, specific for tau nitrated at tyrosine 18 and tyrosine 29, respectively. In the present experiments, Tau-nY18 did not label the classical pathological lesions of CBD or PSP but did label the neuronal lesions associated with PiD to a limited extent. In contrast, Tau-nY29 revealed some, but not all classes of tau inclusions associated with both CBD and PSP but ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5389887 Sat, 05 Nov 2011 17:08:00 +0100 5389887 http://www.medworm.com/index.php?rid=5365403&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq49321905672435g%2F In conclusion, we report multiple lines of evidence that Fas/FasL activation plays a pivotal role in mediating apoptosis, the inflammatory response and neurodegeneration after SCI, providing a compelling rationale for therapeutically targeting Fas in human SCI. Content Type Journal ArticleCategory Original PaperPages 1-15DOI 10.1007/s00401-011-0882-3Authors Wen Ru Yu, Division of Genetics and Development, Toronto Western Research Institute and Krembil Neuroscience Centre, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, CanadaMichael G. Fehlings, Division of Neurosurgery, Toronto Western Research Institute and Krembil Neuroscience Centre, The Toronto Western Hospital, University Health Network, Room 4W-449, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5365403 Sat, 29 Oct 2011 05:50:22 +0100 5365403 http://www.medworm.com/index.php?rid=5365404&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1677532115m2825%2F This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation. Content Type Journal ArticleCategory Original PaperPages 1-12DOI 10.1007/s00401-011-0895-yAuthors Natacha Teissier, Pediatric ENT Department, Robert Debré Hospital, APHP, Paris, FranceAnne-Lise Delezoide, Department of Developmental Biology, Robert Debré Hospital, APHP, Paris, FranceAnne-Elisabeth Mas, Department of Pathology, Béclère Hospital, APHP, Clamart, Fr... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5365404 Fri, 28 Oct 2011 05:49:06 +0100 5365404 http://www.medworm.com/index.php?rid=5365405&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4w1m151347m25k26%2F Content Type Journal ArticleCategory CorrespondencePages 1-3DOI 10.1007/s00401-011-0894-zAuthors B. K. Kleinschmidt-DeMasters, Department of Pathology, UCHSC, University of Colorado at Denver, Anschutz Medical Campus, 12605 E. 16th Avenue, MS F768, Aurora, CO 80045, USAArianne Boylan, Department of Pathology, UCHSC, University of Colorado at Denver, Anschutz Medical Campus, 12605 E. 16th Avenue, MS F768, Aurora, CO 80045, USAKelley Capocelli, Department of Pathology, Children’s Hospital Colorado, 13123 E. 16th Avenue, Aurora, CO 80045, USAPhilip J. Boyer, Department of Pathology, UCHSC, University of Colorado at Denver, Anschutz Medical Campus, 12605 E. 16th Avenue, MS F768, Aurora, CO 80045, USANicholas K. Foreman, Department of Neurooncology, Children’s Hospital Colorado, 13123 E... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5365405 Fri, 28 Oct 2011 05:49:05 +0100 5365405 http://www.medworm.com/index.php?rid=5365406&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk8496xjn4211g147%2F Abstract  In sporadic Alzheimer’s disease (AD), neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. To identify the modification signature associated with tau lesion formation at single amino acid resolution, immunopurified paired helical filaments were isolated from AD brain and subjected to nanoflow liquid chromatography–tandem mass spectrometry analysis. The resulting spectra identified monomethylation of lysine residues as a new tau modification. The methyl-lysine was distributed among seven residues located in the projection and microtubule binding repeat regions of tau protein, with one site, K254, being a substrate for a competing lysine modification, ubiquitylation. To characterize ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5365406 Fri, 28 Oct 2011 05:49:03 +0100 5365406 http://www.medworm.com/index.php?rid=5349690&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F117848tj671473h3%2F Abstract  Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer’s disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1M146L/APP751SL mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Ea... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5349690 Fri, 21 Oct 2011 16:00:19 +0100 5349690 http://www.medworm.com/index.php?rid=5349692&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp07m2828145653t6%2F Content Type Journal ArticleCategory CorrespondencePages 1-2DOI 10.1007/s00401-011-0891-2Authors Manuel Montesinos-Rongen, Department of Neuropathology, University Hospital of Cologne, Cologne, GermanyElzbieta Godlewska, Department of Neuropathology, University Hospital of Cologne, Cologne, GermanyAnna Brunn, Department of Neuropathology, University Hospital of Cologne, Cologne, GermanyOtmar D. Wiestler, German Cancer Research Center, Heidelberg, GermanyReiner Siebert, Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig Holstein, Campus Kiel, Kiel, GermanyMartina Deckert, Department of Neuropathology, University Hospital of Cologne, Cologne, Germany Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5349692 Fri, 21 Oct 2011 16:00:17 +0100 5349692 http://www.medworm.com/index.php?rid=5349691&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg507p3whj8202577%2F Abstract  The apolipoprotein E4 allele (APOE4) contributes to Alzheimer’s disease (AD) risk and APOE2 is protective, but the relevant cellular mechanisms are unknown. We have used flow cytometry analysis to measure apolipoprotein E (apoE) and amyloid beta peptide (Aβ) levels in large populations of synaptic terminals from AD and aged cognitively normal controls, and demonstrate that modest but significant increases in soluble apoE levels accompany elevated Aβ in AD cortical synapses and in an APP/PS1 rat model of AD. Dual labeling experiments document co-localization of apoE and Aβ in individual synapses with concentration of Aβ in a small population of apoE-positive synapses in both AD and controls. Consistent with a clearance role, the apoE level was higher in Aβ-po... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5349691 Fri, 21 Oct 2011 16:00:17 +0100 5349691 http://www.medworm.com/index.php?rid=5338124&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff47222722j437736%2F Abstract  Clinical and pathological evidence supports the notion that corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are distinct, but overlapping neurodegenerative tauopathies. Although both disorders are characterized by abnormal accumulation of 4-repeat tau, they display distinct proteolytic profiles of tau species and they have distinct astrocytic lesions, astrocytic plaques in CBD and tufted astrocytes in PSP. To investigate other differences between these two disorders at the molecular level, we compared the profiles of proteins from caudate nucleus of CBD and PSP by quantitative two-dimensional difference gel electrophoresis. Twenty-one protein spots differentially expressed in CBD and PSP were dissected for mass spectrometry (MS). One of th... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5338124 Wed, 19 Oct 2011 15:44:25 +0100 5338124 http://www.medworm.com/index.php?rid=5338123&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpq5531674827786n%2F In conclusion, expression of BRAF V600E mutant protein occurs in approximately 6% of BM and is consistent in different tumor manifestations of the same patient. Thus, BRAF V600E inhibiting therapies seem feasible in selected BM patients. Immunohistochemical visualization of V600E-mutant BRAF protein is a promising tool for patient stratification. An integrated approach combining both, VE1 immunohistochemistry and genetic analysis may increase the diagnostic accuracy of BRAF mutation analysis. Content Type Journal ArticleCategory Original PaperPages 1-11DOI 10.1007/s00401-011-0887-yAuthors David Capper, Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University, Im Neuenheimer Feld 220/221, 69120 Heidelberg, GermanyAnna Sophie Berghoff, Department of Medicine ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5338123 Wed, 19 Oct 2011 15:44:25 +0100 5338123 http://www.medworm.com/index.php?rid=5338125&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm316582061827g30%2F Abstract  Brain-derived neurotrophic factor (BDNF) is involved in neuronal and glial development and survival. While neurons and astrocytes are its main cellular source in the central nervous system (CNS), bioactive BDNF is also expressed in immune cells and in lesions of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Previous data revealed that BDNF exerts neuroprotective effects in myelin oligodendrocyte glycoprotein-induced EAE. Using a conditional knock-out model with inducible deletion of BDNF, we here show that clinical symptoms and structural damage are increased when BDNF is absent during the initiation phase of clinical EAE. In contrast, deletion of BDNF later in the disease course of EAE did not result in significant chang... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5338125 Wed, 19 Oct 2011 05:54:45 +0100 5338125 http://www.medworm.com/index.php?rid=5338126&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F53579r2l1352w328%2F Content Type Journal ArticleCategory CorrespondencePages 1-2DOI 10.1007/s00401-011-0889-9Authors Kurt A. Jellinger, Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5338126 Tue, 18 Oct 2011 15:56:09 +0100 5338126 http://www.medworm.com/index.php?rid=5325364&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbk820452206241p4%2F Content Type Journal ArticleCategory CorrespondencePages 1-3DOI 10.1007/s00401-011-0886-zAuthors Benjamin Ellezam, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USABrett J. Theeler, Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USARajyalakshmi Luthra, Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USAAdekunle M. Adesina, Department of Pathology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USAKenneth D. Aldape, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USAMark R. Gilbert, Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Journal Acta Neuropatho... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5325364 Thu, 13 Oct 2011 15:50:18 +0100 5325364 http://www.medworm.com/index.php?rid=5316864&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmn2x0g3n44u81438%2F Abstract  In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood–brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition,... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5316864 Sat, 08 Oct 2011 15:44:51 +0100 5316864 http://www.medworm.com/index.php?rid=5316865&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb6m6610416w014g3%2F Content Type Journal ArticleCategory CorrespondencePages 1-2DOI 10.1007/s00401-011-0885-0Authors Jens Schittenhelm, Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tubingen, Tübingen, GermanyMichel Mittelbronn, Neurological Institute, Edinger Institute, University of Frankfurt, Frankfurt, GermanyRichard Meyermann, Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tubingen, Tübingen, GermanyArthur Melms, Department of Neurology, University of Tubingen, Tübingen, GermanyMarcos Tatagiba, Department of Neurosurgery, University of Tubingen, Tübingen, GermanyDavid Capper, Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany Journal Acta Neuropathol... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5316865 Sat, 08 Oct 2011 05:51:50 +0100 5316865 http://www.medworm.com/index.php?rid=5298200&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff1214621w81tu886%2F Abstract  GABAergic interneurons synchronize network activities and monitor information flow. Post-mortem studies have reported decreased densities of cortical interneurons in schizophrenia (SZ) and bipolar disorder (BPD). The entorhinal cortex (EC) and the adjacent subicular regions are a hub for integration of hippocampal and cortical information, a process that is disrupted in SZ. Here we contrast and compare the density of interneuron populations in the caudal EC and subicular regions in BPD type I (BPD-I), SZ, and normal control (NC) subjects. Post-mortem human parahippocampal specimens of 13 BPD-I, 11 SZ and 17 NC subjects were used to examine the numerical density of parvalbumin-, somatostatin- or calbindin-positive interneurons. We observed a reduction in the numeri... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5298200 Tue, 04 Oct 2011 05:50:24 +0100 5298200 http://www.medworm.com/index.php?rid=5298201&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx55586w236w0p1q1%2F Abstract  Cortical neuron death is prevalent by 9 months in rTg(tauP301L)4510 tau mutant mice (TG) and surviving pyramidal cells exhibit dendritic regression and spine loss. We used whole-cell patch-clamp recordings to investigate the impact of these marked structural changes on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) of layer 3 pyramidal cells in frontal cortical slices from behaviorally characterized TG and non-transgenic (NT) mice at this age. Frontal lobe function of TG mice was intact following a short delay interval but impaired following a long delay interval in an object recognition test, and cortical atrophy and cell loss were pronounced. Surviving TG cells had significantly reduced dendritic diameters, total spine densit... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5298201 Tue, 04 Oct 2011 05:50:23 +0100 5298201 http://www.medworm.com/index.php?rid=5298202&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Few0341tg86n8x245%2F Abstract  TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer’s disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down’s Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD pat... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5298202 Tue, 04 Oct 2011 05:50:21 +0100 5298202 http://www.medworm.com/index.php?rid=5287454&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj42116235443j803%2F Abstract  Risks associated with brain biopsy limit availability of tissues and the role of brain biopsy in diagnosing neurodegeneration is unclear. We developed a simulated brain biopsy paradigm to comprehensively evaluate potential accuracy of detecting neurodegeneration in biopsies. Postmortem tissue from the frontal, temporal and parietal cortices and basal ganglia from 73 cases including Alzheimer’s disease (AD), Lewy body disease (LBD), frontotemporal lobar degeneration-TDP43 (FTLD-TDP), multiple system atrophy (MSA), Pick’s disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were evaluated using H&E and immunostains. Brain biopsy was simulated in a blinded manner by masking each slide with opaque tape except for an area measurin... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5287454 Fri, 30 Sep 2011 05:53:13 +0100 5287454 http://www.medworm.com/index.php?rid=5287455&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr372542245447q65%2F Abstract  Alzheimer disease (AD) is a chronic, progressive disorder with an average disease progression of 7–10 years. However, the histopathological hallmark lesions of this disease, the extracellular Aβ plaques and the intraneuronal neurofibrillary tangles, start as early as childhood in the affected individuals. AD is multifactorial and probably involves many different etiopathogenic mechanisms. Thus, while AD offers a wide window of opportunity that practically includes the whole life span of the affected individuals, and numerous therapeutic targets, the multifactorial nature of this disease also makes the selection of the therapeutic targets an immensely challenging task. In addition to β-amyloidosis and neurofibrillary degeneration, the AD brain also is comp... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5287455 Fri, 30 Sep 2011 05:53:11 +0100 5287455 http://www.medworm.com/index.php?rid=5262589&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4810772lkkg31410%2F Abstract  The “Shaken Baby” syndrome (SBS) is the subject of intense controversy; the diagnosis has in the past depended on the triad of subdural haemorrhage (SDH), retinal haemorrhage and encephalopathy. While there is no doubt that infants do suffer abusive injury at the hands of their carers and that impact can cause catastrophic intracranial damage, research has repeatedly undermined the hypothesis that shaking per se can cause this triad. The term non-accidental head injury has therefore been widely adopted. This review will focus on the pathology and mechanisms of the three physiologically associated findings which constitute the “triad” and are seen in infants suffering from a wide range of non-traumatic as well as traumatic conditions. “Sub” dural bleedi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5262589 Sat, 24 Sep 2011 05:43:16 +0100 5262589 http://www.medworm.com/index.php?rid=5252073&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft106822313578t0j%2F Abstract  The last three decades have seen major advances in the understanding of paraneoplastic and idiopathic autoimmune disorders affecting the central nervous system (CNS). Neural-specific autoantibodies and their target antigens have been discovered, immunopathology and neuroimaging patterns recognized and pathogenic mechanisms elucidated. Disorders accompanied by autoantibody markers of neural peptide-specific cytotoxic effector T cells [such as anti-neuronal nuclear antibody type 1 (ANNA-1, aka anti-Hu), Purkinje cell antibody type 1 (PCA-1, aka anti-Yo) and CRMP-5 IgG] are generally poorly responsive to immunotherapy. Disorders accompanied by neural plasma membrane-reactive autoantibodies [the effectors of synaptic disorders, which include antibodies targeting volta... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5252073 Thu, 22 Sep 2011 06:38:59 +0100 5252073 http://www.medworm.com/index.php?rid=5252074&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe1r242un1722211u%2F Abstract  Intra-muscle fiber accumulation of ubiquitinated protein aggregates containing several conformationally modified proteins, including amyloid-β and phosphorylated tau, is characteristic of the pathologic phenotype of sporadic inclusion-body myositis (s-IBM), the most common progressive degenerative myopathy of older persons. Abnormalities of protein-degradation, involving both the 26S proteasome and autophagic-lysosomal pathways, were previously demonstrated in s-IBM muscle. NBR1 is a ubiquitin-binding scaffold protein importantly participating in autophagic degradation of ubiquitinated proteins. Whereas abnormalities of p62, a ubiquitin-binding protein, were previously described in s-IBM, abnormalities of NBR1 have not been reported in s-IBM. We have now identifi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5252074 Tue, 20 Sep 2011 15:45:54 +0100 5252074 http://www.medworm.com/index.php?rid=5252075&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwl0479h3523512u7%2F In conclusion, GVD affects neurons in a hierarchical sequence that allows the distinction of five stages. The topographic distribution of GVD restricted to regions involved in response to chronic stress could indicate a link between GVD and chronically stressful influences. Moreover, the association of the GVD stages with those of AD-related pathology but not with other neurodegenerative disorders points to a possible role of GVD and the response to chronic stress in the pathogenesis of AD. Content Type Journal ArticleCategory Original PaperPages 1-13DOI 10.1007/s00401-011-0871-6Authors Dietmar Rudolf Thal, Laboratory of Neuropathology, Institute of Pathology, Center for Clinical Research, University of Ulm, Ulm, GermanyKelly Del Tredici, Department of Neurology, University of U... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5252075 Tue, 20 Sep 2011 15:45:53 +0100 5252075 http://www.medworm.com/index.php?rid=5252076&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F192r87p052557677%2F Content Type Journal ArticleCategory CorrespondencePages 1-1DOI 10.1007/s00401-011-0868-1Authors Kurt A. Jellinger, Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5252076 Tue, 20 Sep 2011 05:51:00 +0100 5252076 http://www.medworm.com/index.php?rid=5239944&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw7772x1023008456%2F Abstract  Melanocortins produce neuroprotection against ischemic stroke with subsequent long-lasting functional recovery, through melanocortin MC4 receptor activation. Here we investigated whether the long-lasting beneficial effect of melanocortins in stroke conditions is associated with a stimulation of neurogenesis. Gerbils were subjected to transient global cerebral ischemia by occluding both common carotid arteries for 10 min; then, they were prepared for 5-bromo-2′-deoxyuridine (BrdU) labeling of proliferating cells. Delayed treatment (up to 9 h after the ischemic injury) for 11 days with the melanocortin analog [Nle4,d-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) improved learning and memory throughout the 50-day observation period. Immunohistoch... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5239944 Sat, 17 Sep 2011 05:49:06 +0100 5239944 http://www.medworm.com/index.php?rid=5228079&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn472014767u5464l%2F Content Type Journal ArticleCategory CorrespondencePages 1-4DOI 10.1007/s00401-011-0872-5Authors George M. Ibrahim, Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, CanadaAnnie Huang, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, CanadaWilliam Halliday, Division of Pathology, The Hospital for Sick Children, Toronto, ON, CanadaPeter B. Dirks, Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, CanadaDavid Malkin, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, CanadaBerivan Baskin, Division of Molecular Genetics, The Hospital for Sick Children, Toronto, ON, CanadaMary Shago, Division of Molecular Genetics, The Hospital for Sick Children, Toronto, ON, CanadaCynthia Hawkins, Division o... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5228079 Thu, 15 Sep 2011 05:53:52 +0100 5228079 http://www.medworm.com/index.php?rid=5228080&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F94v22084q3633746%2F Abstract  Neurons are very sensitive to DNA damage induced by endogenous and exogenous genotoxic agents, as defective DNA repair can lead to neurodevelopmental disorders, brain tumors and neurodegenerative diseases with severe clinical manifestations. Understanding the impact of DNA damage/repair mechanisms on the nuclear organization, particularly on the regulation of transcription and cell cycle, is essential to know the pathophysiology of defective DNA repair syndromes. In this work, we study the nuclear architecture and spatiotemporal organization of chromatin compartments involved in the DNA damage response (DDR) in rat sensory ganglion neurons exposed to X-ray irradiation (IR). We demonstrate that the neuronal DDR involves the formation of two categories of DNA-damage... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5228080 Wed, 14 Sep 2011 05:44:09 +0100 5228080 http://www.medworm.com/index.php?rid=5228081&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq727218x6472u78j%2F Content Type Journal ArticleCategory CorrespondencePages 1-1DOI 10.1007/s00401-011-0870-7Authors Gabor G. Kovacs, Institute of Neurology, Medical University Vienna, AKH 4J, Währinger Gürtel 18-20, 1097 Vienna, AustriaHerbert Budka, Institute of Neurology, Medical University Vienna, AKH 4J, Währinger Gürtel 18-20, 1097 Vienna, Austria Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5228081 Wed, 14 Sep 2011 05:44:08 +0100 5228081 http://www.medworm.com/index.php?rid=5171261&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh48844220t405323%2F Abstract  The reasons for the selective vulnerability of distinct neuronal populations in neurodegenerative disorders are unknown. The cholinergic neurons of the basal forebrain are vulnerable to pathology and loss early in Alzheimer’s disease and in a number of other neurodegenerative disorders of the elderly. In the primate, including man, these neurons are rich in the calcium buffer calbindin-D28K. Here, we confirm that these neurons undergo a substantial loss of calbindin in the course of normal aging and report a further loss of calbindin in Alzheimer’s disease both at the level of RNA and protein. Significantly, cholinergic neurons that had lost their calbindin in the course of normal aging were those that selectively degenerated in Alzheimer’s disease. Furthermo... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5171261 Fri, 26 Aug 2011 16:17:09 +0100 5171261 http://www.medworm.com/index.php?rid=5164379&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1k315lv50525634%2F Abstract  Incompletely resectable ependymomas are associated with poor prognosis despite intensive radio- and chemotherapy. Novel treatments have been difficult to develop due to the lack of appropriate models. Here, we report on the generation of a high-risk cytogenetic group 3 and molecular group C ependymoma model (DKFZ-EP1NS) which is based on primary ependymoma cells obtained from a patient with metastatic disease. This model displays stem cell features such as self-renewal capacity, differentiation capacity, and specific marker expression. In vivo transplantation showed high tumorigenic potential of these cells, and xenografts phenotypically recapitulated the original tumor in a niche-dependent manner. DKFZ-EP1NS cells harbor transcriptome plasticity, en... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5164379 Tue, 23 Aug 2011 15:52:56 +0100 5164379 http://www.medworm.com/index.php?rid=5164380&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4723254hj7q18h20%2F Abstract  Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This eff... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5164380 Tue, 23 Aug 2011 15:52:55 +0100 5164380 http://www.medworm.com/index.php?rid=5147697&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0p3286663831302%2F Abstract  Subjects with Down syndrome (DS) inevitably develop histopathological features pathognomonic of Alzheimer’s disease (AD), and DS can therefore be considered a human model of AD. Similar to AD, microglial activation has been reported in DS and the idea that detrimental neuroinflammation plays a key role in the pathogenesis of neurodegeneration is firmly embedded. However, recent work from this laboratory has offered evidence for an alternative view regarding the role of microglial cells in AD pathogenesis by showing presence of dystrophic (senescent) rather than activated microglia in both the AD and DS brain. In this report, we build on previously published observations in human brain and offer a detailed analysis of microglial senescent pathology in the tempora... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5147697 Wed, 17 Aug 2011 05:56:50 +0100 5147697 http://www.medworm.com/index.php?rid=5147698&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjq548057701527n4%2F Abstract  The term frontotemporal lobar degeneration (FTLD) describes a group of disorders that are subdivided by the presence of one of a number of pathological proteins identified in the inclusion bodies observed post-mortem. The FUS variant is defined by the presence of the fused in sarcoma protein (FUS) in the pathological inclusions. However, similar to other FTLDs, the disease pathogenesis of FTLD-FUS remains largely poorly understood. Here we present data that the protein transportin1 (TRN1) is abundant in the FUS-positive inclusions. TRN1, the protein product of the TNP01 gene, is responsible for shuttling proteins containing an M9 nuclear localisation signal between the nuclear and cytoplasmic compartments. RNA interacting proteins, including FUS, have been implica... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5147698 Wed, 17 Aug 2011 05:56:49 +0100 5147698 http://www.medworm.com/index.php?rid=5121132&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy6568806843k0231%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00401-011-0862-7Authors Yasuko Toyoshima, Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, Chuo-ku, Niigata 951-8585, JapanHajime Tanaka, Department of Neurology, Shinrakuen Hospital, Niigata, JapanMitsuteru Shimohata, Department of Neurology, Shinrakuen Hospital, Niigata, JapanKakuhei Kimura, Department of Pathology, Shinrakuen Hospital, Niigata, JapanTakashi Morita, Department of Pathology, Shinrakuen Hospital, Niigata, JapanAkiyoshi Kakita, Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, Chuo-ku, Niigata 951-8585, JapanHitoshi Takahashi, Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, Chuo-ku, Niigata 951... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5121132 Wed, 10 Aug 2011 15:49:28 +0100 5121132 http://www.medworm.com/index.php?rid=5111382&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F380t308768641820%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s00401-011-0859-2Authors Marie Christine Bernardo, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAJonathan Graff-Radford, Department of Neurology, Mayo Clinic, Rochester, MN, USAJoshua Menke, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAChristopher Hallemeier, Department of Neurology, Mayo Clinic, Rochester, MN, USAChristopher J. Boes, Department of Neurology, Mayo Clinic, Rochester, MN, USAMark Lewis, Department of Neurology, Mayo Clinic, Rochester, MN, USABernd Scheithauer, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USACaterina Giannini, Department of Labo... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5111382 Sat, 06 Aug 2011 05:52:52 +0100 5111382 http://www.medworm.com/index.php?rid=5089700&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa2g136nt0742218r%2F Abstract  Previous studies of Aβ plasma as a biomarker for Alzheimer’s disease (AD) obtained conflicting results. We here included 715 subjects with baseline Aβ1-40 and Aβ1-42 plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and Aβ1-42 measures in cerebrospinal fluid (CSF). Association between Aβ and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma Aβ. The effect of age differed according to AD stage. Plasma Aβ1-42 showed mild correlation with other biomarkers o... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5089700 Fri, 29 Jul 2011 16:07:26 +0100 5089700 http://www.medworm.com/index.php?rid=5064906&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fuv7001715r217213%2F Abstract  Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder generally presenting with intention tremor and gait ataxia, but with a growing list of co-morbid medical conditions including hypothyroidism, hypertension, peripheral neuropathy, and cognitive decline. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in both neurons and astroglia. However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS). To address this issue, we surveyed non-CNS organs in ten human cases with FXTAS and in a CGG repeat knock-in (CGG KI) mouse model known to possess neuronal and astroglial inclusions. We find inclusions in multiple tissues from FXTAS cases and CGG KI mice, in... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5064906 Fri, 22 Jul 2011 17:06:17 +0100 5064906 http://www.medworm.com/index.php?rid=5064907&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F38543407608g506l%2F In conclusion, post-ischemic neurogenesis in ephrin-B3−/− mice is strongly enhanced, but fails to contribute to functional recovery because of caspase-3-mediated aggravation of ischemic injury in these animals. Our results suggest that ephrin-B3 might be an interesting target for overcoming some of the limitations of further cell-based therapies in stroke. Content Type Journal ArticlePages 1-14DOI 10.1007/s00401-011-0856-5Authors Thorsten R. Doeppner, Department of Neurology, University of Duisburg-Essen Medical School, Hufelandstr. 55, 45122 Essen, GermanyEva Bretschneider, Department of Neurology, University of Goettingen Medical School, 37075 Goettingen, GermanyMaria Doehring, Department of Neurology, University of Goettingen Medical School, 37075 Goettingen, GermanyInmacul... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5064907 Thu, 21 Jul 2011 18:04:23 +0100 5064907 http://www.medworm.com/index.php?rid=5064909&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3885645723430366%2F We describe the clinicopathological and biochemical features of two cases with GOIs: one with clinical symptoms suggestive of MND and the other with FTD. Histological changes in our two cases were consistent with their clinical symptoms; the MND case had severe neurodegeneration in the primary motor cortex and corticospinal tract, whereas the FTD case had severe involvement of the frontotemporal cortices and associated white matter. Immunohistochemistry in both cases revealed significant 4-repeat (4R) tau pathology primarily in the form of GOIs, but also in astrocytes and neurons. Astrocytic tau pathology was morphologically similar to that seen in PSP, but in contrast was consistently negative for Gallyas silver staining. Tau-specific western blotting revealed 68, 64 and 35 kDa... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5064909 Wed, 20 Jul 2011 12:08:37 +0100 5064909 http://www.medworm.com/index.php?rid=5064908&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F316411j80546857n%2F We examined in-vivo expression of MIF in 166 gliomas and 23 normal control brains by immunohistochemistry. MIF immunoreactivity was enhanced in neoplastic astrocytes in WHO grade II glioma and increased significantly in higher tumour grades (III–IV). MIF expression was further assessed in 12 glioma cell lines in vitro. Quantitative RT-PCR showed that MIF mRNA expression was elevated up to 800-fold in malignant glioma cells compared with normal brain. This translated into high protein levels as assessed by immunoblotting of total cell lysates and by ELISA-based measurement of secreted MIF. Wild-type p53-retaining glioma cell lines expressed higher levels of MIF, which may be connected with the previously described role of MIF as a negative regulator of wild-type p53 signalling in t... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5064908 Wed, 20 Jul 2011 12:08:37 +0100 5064908 http://www.medworm.com/index.php?rid=5041734&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg76w7750660pj738%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00401-011-0855-6Authors Jason T. Huse, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAKhedoudja Nafa, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USANeerav Shukla, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAEdward R. Kastenhuber, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAEhud Lavi, Department of Pathology, New York Presbyterian Hospital, New York, NY, USACyrus V. Hedvat, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAMarc Ladanyi, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAMarc K. ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5041734 Thu, 14 Jul 2011 06:01:45 +0100 5041734 http://www.medworm.com/index.php?rid=5022567&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F267148j2827u684q%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00401-011-0854-7Authors Abir Mukherjee, Department of Pathology and Laboratory Medicine, The Methodist Hospital, 6565 Fannin, M227, Houston, TX 77030, USAJo Elle G. Peterson, Department of Pathology and Laboratory Medicine, The Methodist Hospital, 6565 Fannin, M227, Houston, TX 77030, USAGlenn Sandberg, Harris County Institute of Forensic Science, Houston, TX 77054, USAHidehiro Takei, Department of Pathology and Laboratory Medicine, The Methodist Hospital, 6565 Fannin, M227, Houston, TX 77030, USAAdekunle Adesina, Department of Pathology, Texas Children’s Hospital, Houston, TX 77030, USAJ. C. Goodman, Departments of Pathology and Neurology, Baylor College of Medicine, Houston, TX 77030, USASuzanne Powell, Department of Pathology and L... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=5022567 Sat, 09 Jul 2011 06:18:15 +0100 5022567 http://www.medworm.com/index.php?rid=4994561&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3n14777n2188ql67%2F Abstract  Abnormal aggregates of the synaptic protein, α-synuclein, are the dominant pathology in syndromes known as the synucleinopathies. The cellular aggregation of the protein occurs in three distinct types of inclusions in three main clinical syndromes. α-Synuclein deposits in neuronal Lewy bodies and Lewy neurites in idiopathic Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), as well as incidentally in a number of other conditions. In contrast, α-synuclein deposits largely in oligodendroglial cytoplasmic inclusions in multiple system atrophy (MSA). Lastly, α-synuclein also deposits in large axonal spheroids in a number of rarer neuroaxonal dystrophies. Disorders are usually defined by their most dominant pathology, but for the synucleinopathies, clin... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4994561 Thu, 30 Jun 2011 17:49:09 +0100 4994561 http://www.medworm.com/index.php?rid=4987505&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4174527678422j44%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00401-011-0853-8Authors Kurt A. Jellinger, Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, AustriaGabor G. Kovacs, Institute of Neurology, Medical University of Vienna, Vienna, Austria Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4987505 Tue, 28 Jun 2011 15:49:53 +0100 4987505 http://www.medworm.com/index.php?rid=4971583&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwm075284x7033027%2F Abstract  White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue dama... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4971583 Fri, 24 Jun 2011 16:03:09 +0100 4971583 http://www.medworm.com/index.php?rid=4971584&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd82v40166449t3w4%2F Abstract  TDP-43 has been implicated in the pathogenesis of amyotrophic lateral sclerosis and other neurodegenerative diseases. Here we demonstrate, using neuronal and spinal cord organotypic culture models, that chronic excitotoxicity, oxidative stress, proteasome dysfunction and endoplasmic reticulum stress mechanistically induce mislocalization, phosphorylation and aggregation of TDP-43. This is compatible with a lack of function of this protein in the nucleus, specially in motor neurons. The relationship between cell stress and pathological changes of TDP-43 also includes a dysfunction in the survival pathway mediated by mitogen-activated protein kinase/extracellular signal-regulated kinases (ERK1/2). Thus, under stress conditions, neurons and other spinal cord cells sh... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4971584 Fri, 24 Jun 2011 16:03:06 +0100 4971584 http://www.medworm.com/index.php?rid=4971585&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F56t654063t175106%2F Abstract  Cerebrovascular lesions related to congophilic amyloid angiopathy (CAA) often accompany deposition of β-amyloid (Aβ) in Alzheimer’s disease (AD), leading to disturbed cerebral blood flow and cognitive dysfunction, posing the question how cerebrovascular pathology contributes to the pathology of AD. To address this question, we characterised the morphology, biochemistry and functionality of brain blood vessels in transgenic arctic β-amyloid (arcAβ) mice expressing human amyloid precursor protein (APP) with both the familial AD-causing Swedish and Arctic mutations; these mice are characterised by strong CAA pathology. Mice were analysed at early, mid and late-stage pathology. Expression of the glucose transporter GLUT1 at the blood–brain barrier (BBB) was si... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4971585 Tue, 21 Jun 2011 18:00:51 +0100 4971585 http://www.medworm.com/index.php?rid=4971586&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw46172xvhwx07470%2F Abstract  Hippocampal pathology was shown to be extensive in multiple sclerosis (MS) and is associated with memory impairment. In this post-mortem study, we investigated hippocampal tissue from MS and Alzheimer’s disease (AD) patients and compared these to non-neurological controls. By means of biochemical assessment, (immuno)histochemistry and western blot analyses, we detected substantial alterations in the cholinergic neurotransmitter system in the MS hippocampus, which were different from those in AD hippocampus. In MS hippocampus, activity and protein expression of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was decreased, while the activity and protein expression of acetylcholinesterase (AChE), the acetylcholine degrading enzyme, was fou... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4971586 Tue, 21 Jun 2011 16:43:20 +0100 4971586 http://www.medworm.com/index.php?rid=4947385&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv552l3w661814855%2F Abstract  Recent integrative genomic approaches have defined molecular subgroups of medulloblastoma that are genetically and clinically distinct. Sonic hedgehog (Shh) medulloblastomas account for one-third of all cases and comprise the majority of infant and adult medulloblastomas. To discern molecular heterogeneity among Shh-medulloblastomas, we analyzed transcriptional profiles from four independent Shh-medulloblastoma expression datasets (n = 66). Unsupervised clustering analyses demonstrated a clear distinction between infant and adult Shh-medulloblastomas, which was reliably replicated across datasets. Comparison of transcriptomes from infant and adult Shh-medulloblastomas revealed deregulation of multiple gene families, including genes implicated in cellular ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4947385 Fri, 17 Jun 2011 10:51:18 +0100 4947385 http://www.medworm.com/index.php?rid=4947386&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc43t2197l0v4652g%2F Abstract  Spinal muscular atrophy (SMA) is a neurodegenerative disease resulting from decreased levels of survival motor neuron 1 (SMN1) protein. Reduced SMN1 levels are linked to pathology at neuromuscular junctions (NMJs), which includes decreased vesicle density and organization, decreased quantal release, increased endplate potential duration, and neurofilament (NF) accumulations. This work presents a first study towards defining molecular alterations that may lead to the development of NMJ pathology in SMA. Fast, anterograde transport of synaptic vesicle 2 (SV2-c) and synaptotagmin (Syt1) proteins was reduced 2 days prior to the observed decrease in synaptic vesicle density. Moreover, reduced accumulation of SV2-c or Syt1 was not due to reduced protein expression ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4947386 Fri, 17 Jun 2011 10:51:17 +0100 4947386 http://www.medworm.com/index.php?rid=4924625&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq2878066430mp710%2F In conclusion, although the evidence is just emerging and mostly preliminary, disclosing pericytes’ role in the pathophysiology of CNS diseases may yield exciting developments and novel treatments. Content Type Journal ArticlePages 1-9DOI 10.1007/s00401-011-0847-6Authors Turgay Dalkara, Department of Neurology, Faculty of Medicine and, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, TurkeyYasemin Gursoy-Ozdemir, Department of Neurology, Faculty of Medicine and, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, TurkeyMuge Yemisci, Department of Neurology, Faculty of Medicine and, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, Turkey Journal Acta Neur... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4924625 Wed, 08 Jun 2011 15:46:32 +0100 4924625 http://www.medworm.com/index.php?rid=4915468&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa1842t155278161j%2F Abstract  We investigated a family manifesting amyotrophic lateral sclerosis (ALS) with a heterozygous E478G mutation in the optineurin (OPTN) gene. Clinically, slow deterioration of motor function, mood and personality changes, temporal lobe atrophy on neuroimaging, and bizarre finger deformity were noted. Neuropathologically, TAR DNA-binding protein 43 (TDP-43)-positive neuronal intracytoplasmic inclusions were observed in the spinal and medullary motor neurons. In these cells, the immunoreactivity of nuclear TDP-43 was reduced. Consecutive sections revealed that the inclusions were also reactive with anti-ubiquitin and anti-p62 antibodies, but noticeably negative for OPTN. In addition, TDP-43/p62-positive glial cytoplasmic inclusions (GCIs) were scattered throughout the s... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4915468 Sun, 05 Jun 2011 05:46:46 +0100 4915468 http://www.medworm.com/index.php?rid=4915469&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr1h9864644565qh2%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00401-011-0845-8Authors Ian R. A. Mackenzie, Department of Pathology, University of British Columbia and Vancouver General Hospital, 855 West 12th Avenue, Vancouver, British Columbia V5Z 1M9, CanadaManuela Neumann, Institute of Neuropathology, University Hospital Zurich, Zurich, SwitzerlandAtik Baborie, Department of Neuropathology, Walton Center for Neurology and Neurosurgery, Liverpool, UKDeepak M. Sampathu, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Pennsylvania, PA, USADaniel Du Plessis, Department of Pathology, Hope Hospital, Salford, UKEvelyn Jaros, Department of Neuropathology, Newcastle General Hospital, Newcastle-Upon-Tyne, UKRobert H. Perry, Department of Neuropathology, New... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4915469 Sun, 05 Jun 2011 05:46:44 +0100 4915469 http://www.medworm.com/index.php?rid=4896747&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxx54g7322l22j251%2F Abstract  Lack of frataxin in Friedreich’s ataxia (FRDA) causes a complex neurological and pathological phenotype. Progressive atrophy of the dentate nucleus (DN) is a major intrinsic central nervous system lesion. Antibodies to neuron-specific enolase (NSE), calbindin, glutamic acid decarboxylase (GAD), and vesicular glutamate transporters 1 and 2 (VGluT1, VGluT2) allowed insight into the disturbed synaptic circuitry of the DN. The available case material included autopsy specimens of 24 patients with genetically defined FRDA and 14 normal controls. In FRDA, the cerebellar cortex revealed intact Purkinje cell somata and dendrites as assessed by calbindin immunoreactivity. The DN, however, displayed severe loss of large NSE-reactive neurons. Small neurons remained intact.... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896747 Fri, 03 Jun 2011 05:55:52 +0100 4896747 http://www.medworm.com/index.php?rid=4896748&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe442228q367373ln%2F Abstract  Activating mutations of the serine threonine kinase v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) are frequent in benign and malignant human tumors and are emerging as an important biomarker. Over 95% of BRAF mutations are of the V600E type and specific small molecular inhibitors are currently under pre-clinical or clinical investigation. BRAF mutation status is determined by DNA-based methods, most commonly by sequencing. Here we describe the development of a monoclonal BRAF V600E mutation-specific antibody that can differentiate BRAF V600E and wild type protein in routinely processed formalin-fixed and paraffin-embedded tissue. A total of 47 intracerebral melanoma metastases and 21 primary papillary thyroid carcinomas were evaluated by direct sequencing o... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896748 Fri, 03 Jun 2011 05:55:51 +0100 4896748 http://www.medworm.com/index.php?rid=4896749&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl488322054456465%2F We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Aβ deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendrites markedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumula... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896749 Wed, 01 Jun 2011 06:01:51 +0100 4896749 http://www.medworm.com/index.php?rid=4896750&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0521l8031711v52%2F Abstract  Multiple sclerosis is the major inflammatory condition affecting the central nervous system (CNS) and is characterised by disseminated focal immune-mediated demyelination. Demyelination is accompanied by variable axonal damage and loss and reactive gliosis. It is this pathology that is thought to be responsible for the clinical relapses that often respond well to immunomodulatory therapy. However, the later secondary progressive stage of MS remains largely refractory to treatment and it is widely suggested that accumulating axon loss is responsible for clinical progression. Although initially thought to be a white matter (WM) disease, it is increasingly apparent that extensive pathology is also seen in the grey matter (GM) throughout the CNS. GM pathology is chara... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896750 Fri, 27 May 2011 18:13:45 +0100 4896750 http://www.medworm.com/index.php?rid=4896751&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu553960215345r5g%2F Abstract  Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with variable involvement of other systems. A pathogenetic role of immune-mediated mechanisms has been suggested. We retrospectively analyzed sural nerve pathology and the clinical course in 18 patients with ALS. These patients had undergone sural nerve biopsy because of clinical or neurophysiological signs indicating sensory involvement (ALS+). Eleven of the 18 ALS+ patients had inflammatory cell infiltrates (ALSvasc) resembling infiltrates seen in patients with vasculitic neuropathy. Data were compared with the 7 patients without vasculitic infiltrates (ALSnonvasc) and with those of 16 patients with isolated peripheral nerve vasculitis (NPvasc). Biopsy specimens were processed with standard histol... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896751 Fri, 27 May 2011 18:13:44 +0100 4896751 http://www.medworm.com/index.php?rid=4896752&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv50803240426756l%2F Abstract  Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders. With recent discoveries, the FTLDs have been show to classify nicely into three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS. These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants [behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD)], progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS). Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896752 Wed, 25 May 2011 15:56:53 +0100 4896752 http://www.medworm.com/index.php?rid=4896753&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk328t20260588221%2F Abstract  Mutations in the gene encoding the fused in sarcoma (FUS) protein are responsible for ~3% of familial amyotrophic lateral sclerosis (ALS) and <1% of sporadic ALS (ALS-FUS). Descriptions of the associated neuropathology are few and largely restricted to individual case reports. To better define the neuropathology associated with FUS mutations, we have undertaken a detailed comparative analysis of six cases of ALS-FUS that include sporadic and familial cases, with both juvenile and adult onset, and with four different FUS mutations. We found significant pathological heterogeneity among our cases, with two distinct patterns that correlated with the disease severity and the specific mutation. Frequent basophilic inclusions and round FUS-immunoreactive (FUS-ir) neurona... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4896753 Sat, 21 May 2011 23:21:48 +0100 4896753 http://www.medworm.com/index.php?rid=4856311&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg7247x8002q00685%2F Abstract  In Alzheimer’s disease (AD), lipid alterations are present early during disease progression. As some of these alterations point towards a peroxisomal dysfunction, we investigated peroxisomes in human postmortem brains obtained from the cohort-based, longitudinal Vienna-Transdanube Aging (VITA) study. Based on the neuropathological Braak staging for AD on one hemisphere, the patients were grouped into three cohorts of increasing severity (stages I–II, III–IV, and V–VI, respectively). Lipid analyses of cortical regions from the other hemisphere revealed accumulation of C22:0 and very long-chain fatty acids (VLCFA, C24:0 and C26:0), all substrates for peroxisomal β-oxidation, in cases with stages V–VI pathology compared with those modestly affected (stages... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4856311 Thu, 19 May 2011 05:46:52 +0100 4856311 http://www.medworm.com/index.php?rid=4856312&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy033025g18232k37%2F We describe a unique example of SCO wherein a conventional fascicular texture was seen coexisting with and organically merging into follicle-like arrangements. The sellar tumor of 2.7 × 2.6 × 2.5 cm was transphenoidally resected from a 55-year old female. Preoperative magnetic resonance imaging indicated an isointense, contrast enhancing mass with suprasellar extension. Histology showed multiple rudimentary to well-formed, follicle-like cavities on a classical spindle cell background; while all the participating cells exhibited an SCO immunophenotype, including positivity for S100 protein, vimentin, EMA, Bcl-2, and TTF-1, as well as staining with the antimitochondrial antibody 113-1. Conversely no expression of GFAP, follicular-epithelial cytokeratin, carci... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4856312 Wed, 18 May 2011 06:18:00 +0100 4856312 http://www.medworm.com/index.php?rid=4856313&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp3611622n73lx403%2F Abstract  The suppressor of cytokine signaling 3 (SOCS3) gene is one of eight structurally related genes of the SOCS family and has been suggested to function as a tumor suppressor by inhibition of the JAK/STAT signaling pathway. We investigated 60 human gliomas of different histological types for SOCS3 alterations and found frequent SOCS3 promoter hypermethylation and transcriptional downregulation. However, SOCS3 promoter hypermethylation was virtually absent in primary glioblastomas, which are characterized by frequent epidermal growth factor receptor (EGFR) amplification and overexpression. Assessment of the relationship between SOCS3 and EGFR aberrations revealed that SOCS3 promoter hypermethylation was inversely related to both the EGFR gene dosage as well as the EGFR pro... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4856313 Wed, 18 May 2011 06:17:59 +0100 4856313 http://www.medworm.com/index.php?rid=4833410&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe68h44607q804314%2F Abstract  Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are adult onset neurodegenerative disorders characterised by prominent intracellular α-synuclein aggregates (α-synucleinopathies). The glial contribution to neurodegeneration in α-synucleinopathies was largely underestimated until recently. However, brains of PD and DLB patients exhibit not only neuronal inclusions such as Lewy bodies or Lewy neurites but also glial α-synuclein aggregates. Accumulating experimental evidence in PD models suggests that astrogliosis and microgliosis act as important mediators of neurodegeneration playing a pivotal role in both disease initiation and progression. In MSA, oligodendrocytes are intriguingly affected by aberrant cytoplasmic a... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4833410 Thu, 12 May 2011 19:26:26 +0100 4833410 http://www.medworm.com/index.php?rid=4807654&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe5645018442hj723%2F Abstract  Olfactory dysfunction is a frequent and early feature of patients with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) and is very uncommon in patients with frontotemporal dementia (FTD). Mechanisms underlying this clinical manifestation are poorly understood but the premature deposition of protein aggregates in the olfactory bulb (OB) of these patients might impair its synaptic organization, thus accounting for the smell deficits. Tau, β-amyloid and alpha-synuclein deposits were studied in 41 human OBs with histological diagnosis of AD (n = 24), PD (n = 6), FTD (n = 11) and compared with the OB of 15 control subjects. Tau pathology was present in the OB of all patients, irrespective of th... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4807654 Sat, 07 May 2011 15:45:20 +0100 4807654 http://www.medworm.com/index.php?rid=4791232&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe2w286484498651g%2F Abstract  Dopaminergic (DA) neuron degeneration is a feature of brain aging but is markedly increased in patients with Parkinson’s disease (PD). Recent data indicate elevated metabolic stress as a possible explanation for DA neuron vulnerability. Using laser capture microdissection, we isolated DA neurons from the substantia nigra pars compacta of PD patients, age-matched and young controls to determine transcriptional changes by expression profiling and pathway analysis. We verified our findings by comparison to a published dataset. Parallel processing of isolated neurons and bulk tissue allowed the discrimination of neuronal and glial transcription signals. Our data show that genes known to be involved in neural plasticity, axon and synaptic function, as well as cell fa... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4791232 Tue, 03 May 2011 19:47:29 +0100 4791232 http://www.medworm.com/index.php?rid=4791234&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm63546q51752367m%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00401-011-0829-8Authors Marie Christine Bernardo, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAJonathan Graff Radford, Department of Neurology, Mayo Clinic, Rochester, MN, USAJoshua Menke, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAChristopher Hallemeier, Department of Neurology, Mayo Clinic, Rochester, MN, USAChristopher J. Boes, Department of Neurology, Mayo Clinic, Rochester, MN, USAMark Lewis, Department of Neurology, Mayo Clinic, Rochester, MN, USABernd Scheithauer, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USACaterina Giannini, Department of Labo... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4791234 Tue, 03 May 2011 19:47:28 +0100 4791234 http://www.medworm.com/index.php?rid=4784090&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk32202p145864503%2F Abstract  Amyloid imaging has identified cognitively normal older people with plaques as a group possibly at increased risk for developing Alzheimer’s disease-related dementia. It is important to begin to thoroughly characterize this group so that preventative therapies might be tested. Existing cholinotropic agents are a logical choice for preventative therapy as experimental evidence suggests that they are anti-amyloidogenic and clinical trials have shown that they delay progression of mild cognitive impairment to dementia. A detailed understanding of the status of the cortical cholinergic system in preclinical AD is still lacking, however. For more than 30 years, depletion of the cortical cholinergic system has been known to be one of the characteristic features o... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4784090 Sat, 30 Apr 2011 23:41:13 +0100 4784090 http://www.medworm.com/index.php?rid=4769019&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F62132k156j7359h4%2F Content Type Journal ArticlePages 565-568DOI 10.1007/s00401-011-0827-xAuthors Hans Lassmann, Center for Brain Research, Medical University of Vienna, Vienna, AustriaChristian Bancher, Department of Neurology, Landesklinikum Waldviertel Horn-Allentsteig, Horn, AustriaJohannes Attems, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UKWerner Paulus, Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48129 Münster, Germany Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 Journal Volume Volume 121 Journal Issue Volume 121, Number 5 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4769019 Tue, 26 Apr 2011 15:46:41 +0100 4769019 http://www.medworm.com/index.php?rid=4769020&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F87261713m7u0p332%2F In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. Content Type Journal ArticlePages 571-587DOI 10.1007/s00401-011-0826-yAuthors Peter T. Nelson, Department of Pathology, University of Kentucky, Rm 311, Sanders-Brown Building, 800 S. Limestone, Lexington, KY 40536-0230, USAElizabeth Head, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USAFrederick A. Schmitt, Division of Neuropathology, Department of Neurology, University of Kentucky, Lexington, KY 40536-0230, USAPaulina R. Davis, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USAJanna H. Neltner, Department of Pathology, University of Kentucky, Rm 311, Sand... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4769020 Sun, 24 Apr 2011 05:32:22 +0100 4769020 http://www.medworm.com/index.php?rid=4769021&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff077351147171t21%2F Abstract  There is increasing interest in the early phase of Alzheimer’s disease before severe neuronal dysfunction occurs, but it is still not known when or where in the central nervous system the underlying pathological process begins. In this review, we discuss the idea of possible disease progression from the locus coeruleus to the transentorhinal region of the cerebral cortex via neuron-to-neuron transmission and transsynaptic transport of tau protein aggregates, and we speculate that such a mechanism together with the very long prodromal period that characterizes Alzheimer’s disease may be indicative of a prion-like pathogenesis for this tauopathy. The fact that AT8-immunoreactive abnormal tau aggregates (pretangles) develop within proximal axons of noradrenergic ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4769021 Sun, 24 Apr 2011 05:32:20 +0100 4769021 http://www.medworm.com/index.php?rid=4688084&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj275135731710674%2F Abstract  Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocyti... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4688084 Wed, 06 Apr 2011 06:44:39 +0100 4688084 http://www.medworm.com/index.php?rid=4688085&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8mgm37488235x43k%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00401-011-0823-1Authors Alessandro Simonati, Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Policlinico G.B. Rossi, P.le LA Scuro 10, 37134 Verona, ItalyDenise Cassandrini, Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, ItalyDiana Bazan, Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Policlinico G.B. Rossi, P.le LA Scuro 10, 37134 Verona, ItalyFilippo Maria Santorelli, Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, Italy Journal Acta NeuropathologicaOnline IS... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4688085 Tue, 05 Apr 2011 16:58:20 +0100 4688085 http://www.medworm.com/index.php?rid=4678416&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F917q600376046514%2F Fifty years of Acta Neuropathologica: past, present, and future Content Type Journal ArticlePages 1-2DOI 10.1007/s00401-011-0822-2Authors Werner Paulus, Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48129 Munster, GermanyKurt A. Jellinger, Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4678416 Thu, 31 Mar 2011 17:37:53 +0100 4678416 http://www.medworm.com/index.php?rid=4678417&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqq487nx55r3n0j76%2F Abstract  Behavioral and psychological symptoms are commonly observed in a majority of demented patients at some time during the course of their illness. Many of these psychiatric manifestations, especially those related to mood, may be early expressions of dementia and/or mild cognitive impairment. The literature suggests that behavioral and psychological symptoms of dementia (BPSD) are an integral part of the disease process. The dissociation, in many cases, between BPSD and the rather linear decline in cognitive functions suggests that independent pathophysiological mechanisms give rise to these symptoms. A review of the neuroimaging and neuropathology literature indicates that BPSD are the expression of regional rather than diffuse brain pathology. Psychotic symptoms in... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4678417 Thu, 31 Mar 2011 17:37:52 +0100 4678417 http://www.medworm.com/index.php?rid=4646168&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F51017063h43007v4%2F Abstract  Sporadic tauopathies are characterized by differential cellular and topographical predominance of phospho-tau immunoreactivity and biochemical distinction of the tau protein. Established entities include progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, and argyrophilic grain disease. During a community-based longitudinal study on aging, we detected tau pathologies not compatible with these categories. We immunostained for different phospho-tau epitopes, 4R and 3R tau isoforms, α-synuclein, amyloid-β, and phospho-TDP-43, analyzed the MAPT and ApoE genes, and performed western blotting for the tau protein. The mean age of patients (4 women, 3 men) was 83.8 years. Clinical presentations combined dementia with psychiatric symptoms and... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4646168 Fri, 25 Mar 2011 05:49:59 +0100 4646168 http://www.medworm.com/index.php?rid=4628326&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw46k266016032632%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00401-011-0820-4Authors Antoine Italiano, Laboratory of Solid Tumors Genetics, Faculty of Medicine, Nice University Hospital, Nice, FranceSophie Michalak, Department of Pathology, Centre Paul Papin, Angers, FrancePatrick Soulié, Department of Medical Oncology, Centre Paul Papin, Angers, FranceAnnie-Claude Peyron, Laboratory of Solid Tumors Genetics, Faculty of Medicine, Nice University Hospital, Nice, FranceFlorence Pedeutour, Laboratory of Solid Tumors Genetics, Faculty of Medicine, Nice University Hospital, Nice, France Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4628326 Mon, 21 Mar 2011 18:55:57 +0100 4628326 http://www.medworm.com/index.php?rid=4628327&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5p00586528765h11%2F Abstract  Axial myopathy is a rare neuromuscular disease that is characterized by paraspinal muscle atrophy and abnormal posture, most notably camptocormia (also known as bent spine). The genetic cause of familial axial myopathy is unknown. Described here are the clinical features and cause of late-onset predominant axial myopathy and encephalopathy. A 73-year-old woman presented with a 10-year history of severe paraspinal muscle atrophy and cerebellar ataxia. Her 84-year-old sister also developed late-onset paraspinal muscle atrophy and generalized seizures with encephalopathy. Computed tomography showed severe atrophy and fatty degeneration of their paraspinal muscles. Their mother and maternal aunt also developed bent spines. The existence of many ragged-red fibers and c... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4628327 Mon, 21 Mar 2011 18:55:55 +0100 4628327 http://www.medworm.com/index.php?rid=4617836&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq82x38830242864w%2F Abstract  Frontotemporal lobar degeneration (FTLD) is clinically, pathologically and genetically heterogeneous. Recent descriptions of a pathological sub-type that is ubiquitin positive, TDP-43 negative and immunostains positive for the Fused in Sarcoma protein (FUS) raises the question whether it is associated with a distinct clinical phenotype identifiable on clinical grounds, and whether mutations in the Fused in Sarcoma gene (FUS) might also be associated with FTLD. Examination of a pathological series of 118 cases of FTLD from two centres, showing tau-negative, ubiquitin-positive pathology, revealed FUS pathology in five patients, four classified as atypical FTLD with ubiquitin inclusions (aFTLD-U), and one as neuronal intermediate filament inclusion disease (NIFID). Th... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4617836 Sat, 19 Mar 2011 16:59:49 +0100 4617836 http://www.medworm.com/index.php?rid=4617837&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0hrq6203xl6642h6%2F Abstract  Activation of the MAPK signaling pathway has been shown to be a unifying molecular feature in pilocytic astrocytoma (PA). Genetically, tandem duplications at chromosome 7q34 resulting in KIAA1549–BRAF fusion genes constitute the most common mechanism identified to date. To elucidate alternative mechanisms of aberrant MAPK activation in PA, we screened 125 primary tumors for RAF fusion genes and mutations in KRAS, NRAS, HRAS, PTPN11, BRAF and RAF1. Using microarray-based comparative genomic hybridization (aCGH), we identified in three cases an interstitial deletion of ~2.5 Mb as a novel recurrent mechanism forming BRAF gene fusions with FAM131B, a currently uncharacterized gene on chromosome 7q34. This deletion removes the BRAF N-terminal inhibitory domains, gi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4617837 Sat, 19 Mar 2011 16:59:47 +0100 4617837 http://www.medworm.com/index.php?rid=4597019&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F61142r5h3h57671x%2F In this study, we quantify and identify relationships between the levels of the main pathologic form of phosphorylated α-synuclein over the course of Parkinson’s disease in regions affected early through to end-stage disease. Brain tissue samples from 33 cases at different disease stages and 13 controls were collected through the Australian Network of Brain Banks. 500 mg of frozen putamen (affected preclinically) and frontal cortex (affected late) was homogenized, fractionated and α-synuclein levels evaluated using specific antibodies (syn-1, BD Transduction Laboratories; S129P phospho-α-synuclein, Elan Pharmaceuticals) and quantitative western blotting. Statistical analyses assessed the relationship between the different forms of α-synuclein, compared levels between group... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4597019 Sat, 12 Mar 2011 07:01:27 +0100 4597019 http://www.medworm.com/index.php?rid=4562541&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6478834640567753%2F Abstract  Loss-of-function of the lysosomal enzyme galactosyl-ceramidase causes the accumulation of the lipid raft-associated sphingolipid psychosine, the disruption of postnatal myelination, neurodegeneration and early death in most cases of infantile Krabbe disease. This work presents a first study towards understanding the progression of axonal defects in this disease using the Twitcher mutant mouse. Axonal swellings were detected in axons within the mutant spinal cord as early as 1 week after birth. As the disease progressed, more axonopathic profiles were found in other regions of the nervous system, including peripheral nerves and various brain areas. Isolated mutant neurons recapitulated axonal and neuronal defects in the absence of mutant myelinating glia, sugg... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4562541 Fri, 04 Mar 2011 10:49:00 +0100 4562541 http://www.medworm.com/index.php?rid=4537335&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fap108424q7125779%2F Abstract  Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (3... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4537335 Mon, 28 Feb 2011 16:45:30 +0100 4537335 http://www.medworm.com/index.php?rid=4514257&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx2565024384208u7%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00401-011-0812-4 Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4514257 Mon, 21 Feb 2011 16:56:43 +0100 4514257 http://www.medworm.com/index.php?rid=4514258&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe706186g83l1r115%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00401-011-0811-5Authors Tammaryn Lashley, Department of Molecular Neuroscience, Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG UKJanice L. Holton, Department of Molecular Neuroscience, Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG UKTamas Revesz, Department of Molecular Neuroscience, Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG UK Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica) Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4514258 Mon, 21 Feb 2011 16:56:42 +0100 4514258 http://www.medworm.com/index.php?rid=4498917&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff51797p822u7k7xk%2F Abstract  Diffuse astrocytomas (WHO grade II) typically present as slow-growing tumours showing significant cellular differentiation, but possessing a tendency towards malignant progression. They account for ~10% of all astrocytic tumours, with a peak incidence between 30 and 40 years of age. Median survival is reported as around 6–8 years. Mutations of TP53 and IDH1 have been described as genetic hallmarks, while copy number alterations are also relatively common. However, there is some evidence to suggest that these characteristics may vary with age. Here, we present an integrated clinicopathologic, genomic and transcriptomic analysis suggesting that paediatric and adult tumours are associated with distinct genetic signatures. For example, no childhood tumour s... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4498917 Thu, 17 Feb 2011 08:13:12 +0100 4498917 http://www.medworm.com/index.php?rid=4498918&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwr08369g74761j51%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00401-011-0809-zAuthors Hidefumi Ito, Department of Neurology, Kansai Medical University, Osaka, JapanKengo Fujita, Department of Neurology, Kansai Medical University, Osaka, JapanMasataka Nakamura, Department of Neurology, Kansai Medical University, Osaka, JapanReika Wate, Department of Neurology, Kansai Medical University, Osaka, JapanSatoshi Kaneko, Department of Neurology, Kansai Medical University, Osaka, JapanShoichi Sasaki, Department of Neurology, Tokyo Women’s Medical University, Tokyo, JapanKiyomi Yamane, Department of Neurology, Ohta-Atami Hospital, Koriyama, JapanNaoki Suzuki, Department of Neurology, Tohoku University School of Medicine, Sendai, JapanMasashi Aoki, Department of Neurology, Tohoku University School of Medic... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4498918 Thu, 17 Feb 2011 08:13:11 +0100 4498918 http://www.medworm.com/index.php?rid=4471322&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdv1lnp151u011648%2F Abstract  The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were fi... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4471322 Thu, 10 Feb 2011 19:55:56 +0100 4471322 http://www.medworm.com/index.php?rid=4471323&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv3621n8832602736%2F Abstract  The close correlation between abnormally low pre-mortem cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ1–42) and plaque burden measured by amyloid imaging as well as between pathologically increased levels of CSF tau and the extent of neurodegeneration measured by MRI has led to growing interest in using these biomarkers to predict the presence of AD plaque and tangle pathology. A challenge for the widespread use of these CSF biomarkers is the high variability in the assays used to measure these analytes which has been ascribed to multiple pre-analytical and analytical test performance factors. To address this challenge, we conducted a seven-center inter-laboratory standardization study for CSF total tau (t-tau), phospho-tau (p-tau181) and Aβ1–... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4471323 Thu, 10 Feb 2011 19:55:55 +0100 4471323 http://www.medworm.com/index.php?rid=4471324&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc6g21847k336321n%2F Abstract  A heterogeneous population of ependymal cells lines the brain ventricles. The evidence about the origin and birth dates of these cell populations is scarce. Furthermore, the possibility that mature ependymal cells are born (ependymogenesis) or self-renewed (ependymal proliferation) postnatally is controversial. The present study was designed to investigate both phenomena in wild-type (wt) and hydrocephalic α-SNAP mutant (hyh) mice at different postnatal stages. In wt mice, proliferating cells in the ventricular zone (VZ) were only found in two distinct regions: the dorsal walls of the third ventricle and Sylvian aqueduct (SA). Most proliferating cells were monociliated and nestin+, likely corresponding to radial glial cells. Postnatal cumulative BrdU-labeling sho... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4471324 Thu, 10 Feb 2011 19:55:54 +0100 4471324 http://www.medworm.com/index.php?rid=4461485&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F71206x20310r1uk7%2F Abstract  In the hippocampal formation of Alzheimer’s disease (AD) patients, both focal and diffuse deposits of Aβ peptides appear in a subregion- and layer-specific manner. Recently, pyroglutamate (pGlu or pE)-modified Aβ peptides were identified as a highly pathogenic and seeding Aβ peptide species. Since the pE modification is catalyzed by glutaminyl cyclase (QC) this enzyme emerged as a novel pharmacological target for AD therapy. Here, we reveal the role of QC in the formation of different types of hippocampal pE-Aβ aggregates. First, we demonstrate that both, focal and diffuse pE-Aβ deposits are present in defined layers of the AD hippocampus. While the focal type of pE-Aβ aggregates was found to be associated with the somata of QC-expressing interneurons, the... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4461485 Tue, 08 Feb 2011 13:18:18 +0100 4461485 http://www.medworm.com/index.php?rid=4443109&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk3p641t242564327%2F Abstract  In many instances, nerve biopsy is not necessary in the diagnostic work-up of a peripheral neuropathy. However, histological examination of a tissue sample is still mandatory to show specific lesions in various conditions involving peripheral nerves. As there are fewer laboratories that examine human nerve samples, practitioners including neurologists and general pathologists may not be completely aware of the technical issues and data that are provided by nerve biopsy. Nerve biopsy is considered an invasive diagnostic method, although, its complications are by far less disabling than most of the disorders that lead to its indications. Nevertheless, the decision to perform a nerve biopsy has to be made on a case-by-case basis, and its results must be discussed bet... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4443109 Fri, 04 Feb 2011 03:33:45 +0100 4443109 http://www.medworm.com/index.php?rid=4443110&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg4246803126334n5%2F Abstract  The most common cause of amyotrophic lateral sclerosis (ALS) is mutations in superoxide dismutase-1 (SOD1). Since there is evidence for the involvement of non-neuronal cells in ALS, we searched for signs of SOD1 abnormalities focusing on glia. Spinal cords from nine ALS patients carrying SOD1 mutations, 51 patients with sporadic or familial ALS who lacked such mutations, and 46 controls were examined by immunohistochemistry. A set of anti-peptide antibodies with specificity for misfolded SOD1 species was used. Misfolded SOD1 in the form of granular aggregates was regularly detected in the nuclei of ventral horn astrocytes, microglia, and oligodendrocytes in ALS patients carrying or lacking SOD1 mutations. There was negligible staining in neurodegenerative and non-... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4443110 Thu, 03 Feb 2011 20:51:18 +0100 4443110 http://www.medworm.com/index.php?rid=4443111&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F05784856k3vx55kx%2F Abstract  O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl DNA adducts such as those induced by alkylating agents. Loss of MGMT expression through transcriptional silencing by hypermethylation of its CpG island (CGI) is found in diverse human cancers including glioblastomas. Glioblastomas that have MGMT methylation respond to temozolomide, an alkylating agent, resulting in improved survival. Consequently, assessment of MGMT methylation has become a therapy response and prognostic indicator. However, it is not clear whether the region of the MGMT CGI commonly analysed is the critical region involved in transcriptional control. We measured methylation levels at each CpG site for the entire MGMT CGI using bisulfite modification and pyrosequ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4443111 Thu, 03 Feb 2011 20:51:10 +0100 4443111 http://www.medworm.com/index.php?rid=4430226&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjk87212t35835gq7%2F Abstract  Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors albeit at a low frequency. We analyzed exon 15 of BRAF spanning the V600 locus by direct sequencing in 1,320 adult and pediatric tumors of the nervous system including various types of glial, embryonal, neuronal and glioneuronal, meningeal, adenohypophyseal/sellar, and peripheral nervous system tumors. A total of 96 BRAF mutations were detected; 93 of the V600E type and 3 cases with a three base pair insertion between codons 599 and 600. The highest f... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4430226 Fri, 28 Jan 2011 06:53:11 +0100 4430226 http://www.medworm.com/index.php?rid=4412720&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn40r827440106314%2F We describe a robust method for detecting SHH, WNT, and non-SHH/WNT molecular subgroups in formalin-fixed medulloblastoma samples. In corroborating other studies that indicate the value of combining clinical, pathological, and molecular variables in therapeutic stratification schemes for medulloblastoma, we also provide the first outcome data based on a clinical trial cohort and novel data on how molecular subgroups are distributed across the range of disease. Content Type Journal ArticlePages 1-16DOI 10.1007/s00401-011-0800-8Authors David W. Ellison, Department of Pathology MS# 250, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USAJames Dalton, Department of Pathology MS# 250, St. Jude Children’s Research Hospital, 262 Danny Thomas Place,... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4412720 Tue, 25 Jan 2011 22:13:11 +0100 4412720 http://www.medworm.com/index.php?rid=4401933&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp34765x22qx650p1%2F We report that drainage of small molecular weight dextran along cerebrovascular basement membranes is impaired in the hippocampal capillaries and arteries of 22-month-old wild-type mice compared to 3- and 7-month-old animals, which was associated with age-dependent changes in capillary density. Age-related alterations in the levels of laminin, fibronectin and perlecan in vascular basement membranes were also noted in wild-type mice. Furthermore, dextran was observed in the walls of veins of Tg2576 mice in the presence of CAA, suggesting that deposition of Aβ in vessel walls disrupts the normal route of elimination of solutes from the brain parenchyma. These data support the hypothesis that perivascular solute drainage from the brain is altered both in the ageing brain and as a conse... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4401933 Sat, 22 Jan 2011 20:12:00 +0100 4401933 http://www.medworm.com/index.php?rid=4379275&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flpl514741083m401%2F This study aims to determine the frequency, severity and distribution of PIN1 immunoreactivity and its relationship to NFTs and other neuropathological markers of neurodegeneration such as amyloid-β (Aβ) plaques and transcription-responsive DNA-binding protein of M r 43 kDa (TDP-43). Immunohistochemical analysis of 194 patients (46 with AD, 43 with Parkinson’s disease/dementia with Lewy bodies, 12 with progressive supranuclear palsy/corticobasal degeneration, 36 with frontotemporal lobar degeneration, 21 with motor neuron disease and 34 non-demented (ND) individuals) revealed an increased frequency and severity of PIN1 immunoreactive inclusions in AD as compared to all diagnostic groups (P < 0.001). The hippocampal and cortical distribution of PIN1 granules was ... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4379275 Mon, 17 Jan 2011 20:24:44 +0100 4379275 http://www.medworm.com/index.php?rid=4357308&cid=s_33262_25_f&fid=33262&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb7pn4541q37342k0%2F Abstract  Cyclic GMP (cGMP)-mediated pathways regulate inflammatory responses in immune and CNS cells. Recently, cGMP phosphodiesterase inhibitors such as sildenafil, commonly used to treat sexual dysfunction in humans including multiple sclerosis (MS) patients, have been reported to be neuroprotective in animal models of stroke, Alzheimer’s disease, and focal brain lesion. In this work, we have examined if sildenafil ameliorates myelin oligodendrocyte glycoprotein peptide (MOG35–55)-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show for the first time that treatment with sildenafil after disease onset markedly reduces the clinical signs of EAE by preventing axonal loss and promoting remyelination. Furthermore, sildenafil decreases CD3+... Acta Neuropathologica journals http://www.medworm.com/rss/comments.php?id=4357308 Fri, 14 Jan 2011 16:32:57 +0100 4357308