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Transformative neuropathology is redefining human brain research by integrating foundational descriptive pathology with advanced methodologies. These approaches, spanning multi-omics studies and machine learning applications, will drive discovery for the identification of biomarkers, therapeutic targets, and complex disease patterns through comprehensive analyses of postmortem human brain tissue. Yet critical challenges remain, including the sustainability of brain banks, expanding donor...

Aging-related declines in energy metabolism represent a key risk factor for the development of amyloid pathology, the earliest hallmark of Alzheimer's disease. Aging also contributes to the emergence of the second major hallmark, tau pathology, whose propagation is facilitated by pre-existing amyloid accumulation. The overlap of amyloid and tau pathologies ultimately leads to neurodegeneration and the onset of Alzheimer's disease-the most prevalent form of dementia. Recent findings underscore a...

CONCLUSIONS: The mortality risk is elevated among frail elderly individuals, particularly those who are underweight. Overweight exhibits a protective role in both frail and non-frail elderly persons.

In Parkinson's disease (PD), α-synuclein aggregation in striatal synapses is hypothesised to trigger a cascade of events leading to synaptic loss and cortical Lewy body (LB) pathology. Using multiplex immunofluorescence and confocal microscopy on 69 brains spanning Braak stages 0-6-including controls, incidental LB disease (iLBD), and PD-we show that phosphorylated (pSer129) α-synuclein is enriched in putaminal dopaminergic synapses already in early disease stages, and associates with...

Natural language processing (NLP) can expand the utility of clinical records data in dementia research. We deployed NLP algorithms to detect core features of dementia with Lewy bodies (DLB) and applied those to a large database of patients diagnosed with dementia in Alzheimer's disease (AD) or DLB. Of 14,329 patients identified, 4.3% had a diagnosis of DLB and 95.7% of dementia in AD. All core features were significantly commoner in DLB than in dementia in AD, although 18.7% of patients with...

DNMT3A is a critical regulator of hematopoietic stem cell (HSC) fate decisions and the most recurrently mutated gene in human clonal hematopoiesis (CH). DNMT3A is described as a DNA methyltransferase enzyme, but cells with DNMT3A loss of function show minor changes in DNA methylation that do not correlate with altered gene expression. To explore the possibility that Dnmt3a has DNA-methylation-independent functions in HSCs, we created an allelic series of mice with varying levels of...

CONCLUSION: Fall history independently predicts stroke risk in individuals with PS, highlighting the potential of fall prevention to reduce stroke burden in this population. This study provides novel evidence of a prolonged stroke risk trajectory in Asian PS cohorts, complementing Western studies focused on short-term post-fall risks. The study has several limitations. Self-reported falls may introduce recall bias and lack mechanistic details. Unmeasured confounders such as diet and medication...

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Skeletal muscle characteristics play a crucial role in understanding physical capacity, overall health, and outcomes. Muscle strength and muscle mass are key indicators of muscular function and sarcopenia. While previous research has explored biceps brachii muscle characteristics in isolation, there is a notable gap in comprehensive studies examining the direct correlation between biceps brachii muscle thickness (BMT), as measured by ultrasound, and muscle strength. In community-dwelling elderly...

CHI3L1/YKL-40 is an astrocyte-secreted glycoprotein recognized as a biomarker of CNS inflammation and implicated in Alzheimer's disease (AD) cognitive decline. However, its precise pathological role remains unclear. Here, we investigate CHI3L1's function and its therapeutic potential in AD using both human induced pluripotent stem cell-derived neurogenesis models and in vivo conditional AD mouse models, with astrocyte-specific CHI3L1 knockout, alongside 5XFAD mice. Our data reveal that CHI3L1...

Osteoarthritis (OA) is a challenging degenerative joint disease with limited treatment options. Subchondral bone plays a critical role in maintaining joint homeostasis and influencing OA progression. Here, we investigated the role of senescence in mesenchyme-derived stem/progenitor cells (MDSPCs) during OA progression, aiming to identify potential therapeutic targets. Histopathological evaluations and bioinformatic analyses of OA samples from both humans and mice revealed that EGFR^(+) MDSPCs...

Mindfulness cultivates awareness, presence, and non-judgmental acceptance, enhancing overall well-being. Inflammaging, linking age and aged-related diseases, manifests through heightened levels of IL-6, TNF-α, and CRP, impacting aging indicators like TA, TL, PWV, and FMD. To assess how mindfulness-based interventions (MBIs) affect inflammaging, a search was conducted in PubMed, Web of Science, Cochrane Central Register, and ProQuest Dissertation & Theses Global up to March 2024. Criteria...

INTRODUCTION: The cerebellum is essential for motor control and learning, relying on structural and functional integrity. Age-related atrophy leads to Purkinje cell loss, but subtle neurochemical changes in GABA, Glx (glutamate + glutamine), and glutathione (GSH) may precede degeneration and contribute to motor decline.