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Plasma phosphorylated tau 217 (pTau217) is an excellent biomarker of Alzheimer's disease (AD) pathology, but it remains uncertain whether pTau217 can predict amyloid-β (Aβ) and tau accumulation prior to Aβ positron emission tomography (PET) positivity. Here, we leverage data from a well-characterized prospective cohort of cognitively unimpaired older adults to examine mass spectrometry-based plasma %pTau217 (pTau217/non-phosphorylated-Tau217×100) relative to changes in Aβ/tau PET and cognition....

Astrocytes are key partners for neurons and can impact diseases such as Alzheimer's disease (AD), as they exhibit multiple reactive changes. Recent single cell/nucleus genomics analyses evidence astrocyte subpopulations coexisting in normal and AD brains. However, the signaling cascades controlling them, their functional characteristics and roles in AD are still unknown. Here, thanks to astrocyte-specific reporters for STAT3 and NF-kB signaling pathways, two regulators of astrocyte reactivity,...

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Cognitive flexibility is an executive function that enables adapting behaviour to a changing environment and is thus critical for daily life. The degree of its preservation upon healthy aging and the neural mechanisms underlying it are still a matter of debate. To investigate the electrophysiological correlates of cognitive flexibility in older age, we measured cognitive flexibility in 99 young (24.75 ± 4.45 years) and 83 older adults (69.19 ± 6.25) using electroencephalography (EEG). Compared...

Mutations in DNA damage repair (DDR) genes lead to genomic instability, driving a range of degenerative syndromes. In addition to promoting mutation accumulation, unrepaired DNA damage can leak into the cytosol and activate innate immune-sensing pathways, particularly the cGAS-STING axis. However, the extent to which cGAS causally contributes to organismal pathology in DDR syndromes in vivo remains unresolved. Here, we genetically model ataxia telangiectasia (A-T) and Bloom syndrome in the...

Transmembrane protein 65 (TMEM65) depletion in a patient caused severe mitochondrial encephalomyopathy, highlighting its clinical importance. Recent studies show TMEM65 acts as a mitochondrial Na^(+)/Ca^(2+) exchanger in vitro. Here, we generated conditional Tmem65 knockout mice to define its role in neuromuscular tissues in vivo. Both whole-body and nervous system-specific Tmem65 knockouts exhibited severe growth retardation and seizure-associated sudden death at ~3 weeks, establishing TMEM65...

Although seawater electrolysis holds great promise for green hydrogen production, the persistent challenges of chloride ions (Cl^(-))-induced chemical corrosion and localized acid etching under high potential severely hinder the lifespan of the anode. Herein, we propose that Os nanoparticles anchored on CoP nanowires supported by Ni foam (Os-CoP/NF) acts as a dual-protection anode with proton-buffering and Cl^(-)-repelling capabilities to simultaneously inhibit corrosion during seawater...

Aging is an important risk factor for Parkinson's disease (PD). Characterizing age-related alterations in the nigrostriatal system may help identify early vulnerability prior to overt neurodegeneration. We aimed to delineate aging trajectories of structure and hemodynamics of the nigrostriatal system and examine their associations with motor and cognitive functions. We analyzed 486 healthy adults from Human Connectome Project-Aging dataset, stratified into younger (≤ 60 years) and older (> 60...

Accelerated biological aging has been associated with mortality, but it remains unclear whether longitudinal changes in age acceleration predict long-term mortality risk. In the population-based Dutch Lifelines cohort, we estimated biological age using the Klemera-Doubal method (KDM-BA) and derived KDM-BA acceleration at baseline and follow-up. We examined baseline acceleration (continuous and categorical: < - 1, - 1 to 1 [reference], > 1 year), annual change in acceleration and four aging...

Stroke survivors often face long-term cognitive and motor deficits. Brain age gap (BAG), the difference between chronological age and age estimated based on MRI data, has emerged as a biomarker for neurodegeneration. While prior work links BAG to stroke outcomes, the relationship between BAG and cerebral microbleeds (CMBs), particularly infratentorial CMBs common in hypertensive arteriopathy, remains unclear. The sensorimotor network (SMN) is highly susceptible to both direct and remote injury...

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CONCLUSION: These findings underscore the importance of incorporating physical performance measures and social factors in MCR screening protocols and may inform screening and risk stratification in aging populations.