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Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment
CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked.HIGHLIGHTS: Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. With further research, modulating mGluR5 availability might b...
Source: The Journal of Alzheimers Association - April 18, 2024 Category: Psychiatry Authors: Jie Wang Qi Huang Kun He Junpeng Li Tengfei Guo Yang Yang Zengping Lin Songye Li Greet Vanderlinden Yiyun Huang Koen Van Laere Yihui Guan Qihao Guo Ruiqing Ni Binying Li Fang Xie Source Type: research

Cognitively healthy centenarians are genetically protected against Alzheimer's disease
DISCUSSION: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems.HIGHLIGHTS: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls...
Source: The Journal of Alzheimers Association - April 18, 2024 Category: Psychiatry Authors: Niccolo' Tesi Sven van der Lee Marc Hulsman Natasja M van Schoor Martijn Huisman Yolande Pijnenburg Wiesje M van der Flier Marcel Reinders Henne Holstege Source Type: research

Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer's disease trial
We examined plasma amyloid beta 42/40 and positron emission tomography (PET) amyloid eligibility for the ongoing AHEAD Study preclinical AD program (NCT04468659).METHODS: Univariate logistic regression models were used to examine group differences in plasma and PET amyloid screening eligibility.RESULTS: Of 4905 participants screened at time of analysis, 1724 were plasma eligible to continue in screening: 13.3% Hispanic Black, 24.7% Hispanic White, 20.8% non-Hispanic (NH) Asian, 24.7% NH Black, and 38.9% NH White. Plasma eligibility differed across groups in models controlling for covariates (odds ratio from 1.9 to 4.0 comp...
Source: The Journal of Alzheimers Association - April 17, 2024 Category: Psychiatry Authors: Doris Patricia Molina-Henry Rema Raman Andy Liu Oliver Langford Keith Johnson Leona K Shum Crystal M Glover Shobha Dhadda Michael Irizarry Gustavo Jimenez-Maggiora Joel B Braunstein Kevin Yarasheski Venky Venkatesh Tim West Philip B Verghese Robert A Riss Source Type: research

White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old
DISCUSSION: Decreased AQP expression within WMH and proximal NAWM suggest an overwhelmed system wherein water homeostasis is no longer maintained, contributing to WM damage in older individuals.HIGHLIGHTS: Post mortem magnetic resonance imaging (MRI) was used to characterize the pathology of white matter hyperintensities (WMHs) and surrounding normal appearing white matter (NAWM). Stained immunohistochemical (IHC) slides from targeted WMH and NAWM samples were digitized and quantified. WMHs and NAWM were associated with inflammation, demyelination, and gliosis. WMHs and NAWM astrocytic changes included decreased AQP1 and A...
Source: The Journal of Alzheimers Association - April 17, 2024 Category: Psychiatry Authors: Lisa C Silbert Natalie E Roese Victoria Krajbich Justin Hurworth David Lahna Daniel L Schwartz Hiroko H Dodge Randall L Woltjer Source Type: research

MINocyclinE to Reduce inflammation and blood-brain barrier leakage in small Vessel diseAse (MINERVA): A phase II, randomized, double-blind, placebo-controlled experimental medicine trial
DISCUSSION: 11C-PK11195 binding and increased BBB permeability are present in SVD; minocycline did not reduce either process. Whether these pathophysiological mechanisms are disease-causing remains unclear.INTERNATIONAL CLINICAL TRIALS REGISTRY PORTAL IDENTIFIER: ISRCTN15483452 HIGHLIGHTS: We found focal areas of increased microglial signal and increased blood-brain barrier permeability in patients with small vessel disease. Minocycline treatment was not associated with a change in these processes measured using advanced neuroimaging. Blood-brain barrier permeability was dynamic but MRI-derived measurements correlated well...
Source: The Journal of Alzheimers Association - April 17, 2024 Category: Psychiatry Authors: Robin B Brown Daniel J Tozer Laurence Loubi ère Eric L Harshfield Young T Hong Tim D Fryer Guy B Williams Martin J Graves Franklin I Aigbirhio John T O'Brien Hugh S Markus Source Type: research

Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results
DISCUSSION: Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset.HIGHLIGHTS: Gray matter perfusion declines in at-risk genetic frontotemporal dementia (FTD). Regional perfusion decline differs between at-risk genetic FTD subgroups . Hypoperfusion in the left thalamus is common across all presymptomatic groups. Converters exhibit greater right frontal hypoperfusion than non-converters past their expected conversion date. Cerebral hypoperfusion is a potential early biomarker of genetic FTD.PMID:38623902 | DOI:10.1002/alz.13750 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - April 16, 2024 Category: Psychiatry Authors: Maurice Pasternak Saira S Mirza Nicholas Luciw Henri J M M Mutsaerts Jan Petr David Thomas David Cash Martina Bocchetta Maria Carmela Tartaglia Sara B Mitchell Sandra E Black Morris Freedman David Tang-Wai Ekaterina Rogaeva Lucy L Russell Arabella Bouzigu Source Type: research

Anxiety in Alzheimer's disease rats is independent of memory and impacted by genotype, age, sex, and exercise
DISCUSSION: Concluding that while factors such as age, sex, AD genotype, and training status can impact anxiety levels in the TgF344-AD model, anxiety level did not impact memory performance.HIGHLIGHTS: Increased anxiety-like behavior in TgF344-AD rats does not correlate with declines in memory performance. Predictors of higher anxiety-like behaviors in the TgF344-AD rat include age, Alzheimer's disease (AD) genotype, and sex with female AD animals experiencing greater anxiety compared to female wild-type or male AD. Exercise training leads to decreased anxiety-like behaviors in the TgF344-AD rat.PMID:38624069 | DOI:10.100...
Source: The Journal of Alzheimers Association - April 16, 2024 Category: Psychiatry Authors: Danielle C Lopez Zachary J White Stephanie E Hall Source Type: research

Peripheral HMGB1 is linked to O < sub > 3 < /sub > pathology of disease-associated astrocytes and amyloid
DISCUSSION: Astrocytes and peripheral myeloid cells are critical lung-brain axis interactors. HMGB1 loss in peripheral myeloid cells regulates the O3-induced DAA phenotype. These findings demonstrate a mechanism and potential intervention target for air pollution-induced AD pathobiology.HIGHLIGHTS: Astrocytes are part of the lung-brain axis, regulating how air pollution affects plaque pathology. Ozone (O3) astrocyte effects are associated with increased plaques and modified by plaque localization. O3 uniquely disrupts the astrocyte transcriptomic and proteomic disease-associated astrocyte (DAA) phenotype in plaque associat...
Source: The Journal of Alzheimers Association - April 16, 2024 Category: Psychiatry Authors: Chandrama Ahmed Hendrik J Greve Carla Garza-Lombo Jamie A Malley James A Johnson Adrian L Oblak Michelle L Block Source Type: research

Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline
DISCUSSION: Our results elucidate the mechanism of Nr4a1-dependent TrkB regulation in cognition and synaptic function, indicating that Nr4a1 is a target for the treatment of cognitive decline.HIGHLIGHTS: Nr4a1 is reduced in PBMCs and CA1 PyrNs with aging. Nr4a1 ablation in CA1 PyrNs impaired cognition and excitatory synaptic function. Nr4a1 overexpression in CA1 PyrNs ameliorated cognitive impairment of aged mice. Nr4a1 bound to TrkB promoter to enhance transcription. Blocking TrkB function compromised Nr4a1-induced cognitive improvement.PMID:38605605 | DOI:10.1002/alz.13819 (Source: The Journal of Alzheimers Association)
Source: The Journal of Alzheimers Association - April 12, 2024 Category: Psychiatry Authors: Jiang Chen Zhi Zhang Ying Liu Lili Huang Yi Liu Dan Yang Xinyu Bao Pinyi Liu Yuhan Ge Qingqing Li Xin Shu Lushan Xu Yun Stone Shi Xiaolei Zhu Yun Xu Source Type: research