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The genetic architecture of postoperative delirium after major surgery and its relationship with nonpostoperative neurocognitive conditions: A genome-wide association study
CONCLUSIONS: We identified genetic variants associated with increased risk of postoperative delirium. We also found evidence of shared genetic liability with Alzheimer's disease via APOE, complementing recent large-scale studies in all-cause delirium. If validated, the findings have potential clinical applications, including preoperative risk stratification and early identification of pre-clinical Alzheimer's disease risk.
Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification
Phosphorylated-tau 217 (pTau217) is currently the most promising blood-based biomarker for accurately detecting Alzheimer's disease (AD) pathology. However, interference from peripheral tau species in the kidneys or peripheral nerves can hinder diagnostic precision. Recently developed brain-derived pTau217 (BD-pTau217) assays emerge as highly specific tools for detecting AD-related pathological changes in the brain. In this study, we conducted a head-to-head comparison of the NULISAqpcr...
Cellular circadian period and its deviation associate with Alzheimer's pathology and brain aging in cognitively impaired older adults
Circadian rhythm disruption is recognized as a feature of aging and neurodegenerative disease, yet whether intrinsic cellular circadian properties relate to underlying processes in humans remains unknown. We measured intrinsic circadian period and its deviation from 24 h (Δ-period) using ex vivo bioluminescence in dermal fibroblasts from 135 older adults with cognitive complaints. Associations with plasma biomarkers (pTau-217, neurofilament light chain [NfL], and glial fibrillary acidic protein...
Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity
The prevailing view frames microglia and macrophages as guardians against amyloid beta (Aβ) accumulation in Alzheimer's disease (AD). Here, we overturn this paradigm by demonstrating that human phagocytic cells, including differentiated THP-1 macrophages and hESC-derived microglia, are not merely passive responders but active producers of extracellular, seeding-competent Aβ42 fibrils, the amyloid species most strongly linked to parenchymal plaque formation and neurodegeneration. These...
Cellular circadian period and its deviation associate with Alzheimer's pathology and brain aging in cognitively impaired older adults
Circadian rhythm disruption is recognized as a feature of aging and neurodegenerative disease, yet whether intrinsic cellular circadian properties relate to underlying processes in humans remains unknown. We measured intrinsic circadian period and its deviation from 24 h (Δ-period) using ex vivo bioluminescence in dermal fibroblasts from 135 older adults with cognitive complaints. Associations with plasma biomarkers (pTau-217, neurofilament light chain [NfL], and glial fibrillary acidic protein...
Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential
The maintenance of protein homeostasis is essential for neuronal survival and function; however, it progressively declines with age, predisposing the brain to neurodegenerative diseases. Molecular chaperones Hsp70 and Hsp90 are key guardians of proteostasis, pivotally regulating protein folding, refolding, and degradation under both physiological and stress conditions. This review integrates an overview of the structural features, isoforms, and mechanistic interactions of Hsp70 and Hsp90. It...
Gut microbiota and brain aging: a comparative review of African and western populations
As the population ages, cognitive decline and neurodegenerative diseases have become major public health concerns. The human gut microbiota plays a major role in regulating neurodevelopment, neuroinflammation, and cognitive decline through the gut-brain axis. Emerging evidence reveals a possible association between alterations in gut microbial diversity and age-related neurological disorders, including Alzheimer's disease and neurodegeneration. Regional and dietary differences shape the gut...
Erzhi pills: a potential aging-modulating agent targeting immunosenescence in mice
Erzhi Pills (EZP), a traditional Chinese herbal formula, has demonstrated potential aging-modulating properties, while its mechanisms in modulating immunosenescence remain incompletely understood. Two complementary aging murine models were employed to investigate the anti-immunosenescence efficacy of EZP, providing experimental validation for its translational application in delaying age-related immune decline. Morphological and physiological parameters were monitored and thymic/splenic organ...
The protective role of companion animal ownership in cognitive aging: current status of the literature
Cognitive aging reflects underlying biological aging processes and is a key driver of late-life functional outcomes. Emerging evidence indicates that cohabitation with companion animals may influence multiple systemic pathways involved in cognitive aging, yet this potentially modifiable lifestyle factor remains underrecognized. The present narrative review synthesizes current evidence on how companion animals may influence cognitive aging through multilevel pathways, including both direct...
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