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Tau seeds induce neurofibrillary tangle formation across brain regions via individual-specific connectivity

2 weeks ago
The spread of tau pathology across the cerebral cortex is closely tied to cognitive decline in Alzheimer's disease (AD). To investigate mechanisms underlying tau spread, we measured bioactivity of tau seeds from inferior temporal gyrus (ITG) and superior frontal gyrus (SFG) synaptosomes in 128 individuals and demonstrated that tau seed bioactivity associates with tau phosphorylation, neurofibrillary tangles (NFTs), and cognitive impairment. Incorporating genotype data from the same individuals...
Audrey J Weber

Psychological research on Alzheimer's disease in Pakistan: A systematic review of current trends and research gaps

2 weeks ago
Alzheimer's disease (AD) is an escalating public health concern in low- and middle-income countries like Pakistan, with rising prevalence among the aging population. While global research has increasingly addressed the psychological dimensions of AD, Pakistan's contribution remains limited. This systematic review, conducted in accordance with PRISMA guidelines, examines the scope and focus of psychological research on AD in Pakistan. Eleven empirical studies published between 2014 and 2025 were...
Amna Aurooj

Drug repurposing in Alzheimer's disease: Emerging therapeutic strategies and promising candidates

2 weeks ago
Alzheimer's disease is a progressive neurodegenerative disorder, and the most common cause of dementia, which causes 60-70 % of cases worldwide, and its prevalence is increasing by more than 55 million people globally, with an expected increase of 139 million cases by 2050. AD is characterized by Amyloid-β plaque deposition, tau hyperphosphorylation, synaptic dysfunction, neuroinflammation, and oxidative stress, which makes the pathophysiology multifactorial and complex in terms of the...
Pradip S More

The role and therapeutic potential of DNA glycosylases in Alzheimer's disease

2 weeks ago
The aging brain is highly vulnerable to oxidative genomic damage, the accumulation of which is a hallmark of Alzheimer's disease (AD). The base excision repair (BER) pathway, initiated by DNA glycosylases, serves as the primary guardian against such damage. This review synthesizes recent evidence revealing the dual and dynamic roles of key DNA glycosylases including OGG1, MUTYH, MPG, and members of the NEIL family in AD pathogenesis. Beyond canonical repair functions, these enzymes actively...
Xia Zhao

Quantitative ultrasound radiofrequency analysis for monitoring Parkinson's disease

2 weeks ago
Current clinical assessments of Parkinson's disease rely largely on functional scales, which lack sensitivity to subtle muscle alterations. Therefore, developing objective and quantitative tools to support both diagnosis and disease monitoring is needed. Quantitative ultrasound radiofrequency imaging, particularly through Nakagami analysis, offers a non-invasive means of characterizing tissue scattering properties that may reflect Parkinson's disease - related effects. This study aimed to assess...
Baptiste Bizet

Trajectories of plasma and CSF MTBR-tau243 and phosphorylated-tau species across the Alzheimer's disease continuum

2 weeks ago
To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models...
Lyduine E Collij

The rhythm of aging: Stability and drift in the individual rate of senescence

2 weeks ago
Human aging is marked by a steady rise in the risk of dying with age-a process demographers call senescence. Over the past century, life expectancy has risen dramatically, but is this because we are aging slower, or simply starting it later? Vaupel hypothesizes that the pace at which individuals age may be constant, with gains in longevity coming from the delayed onset of senescence rather than its slowing down. We test this idea using a framework that decomposes the pace of senescence into...
Silvio C Patricio

Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators

2 weeks ago
At the blood-tissue interface, vasculature luminal surface is critical for molecular transport, signaling transduction, and cell extravasation. Here, we present a method for proteomic profiling of the vasculature luminal surface in vivo, broadly applicable to any vertebrate. Quantitative mass spectrometry revealed the luminal surface proteome of the mouse brain vasculature and its temporal evolution from development to aging. In vivo genetic perturbation found that the arginine transporter...
Zijian Zhu

Genetic predisposition to hand grip strength predicts cognitive decline

2 weeks ago
Hand grip strength (HGS) is a predictor of cognitive decline in aging. To understand the direct and indirect mechanisms underlying this association, we performed integrative analyses of genetic, cognitive, and autopsy data. A polygenic risk score for HGS (PRS(HGS)) was calculated in two independent studies of aging (total n = 25,227). Cross-sectional and longitudinal modeling, including mediation with physical activity, assessed the effects of PRS(HGS) on cognitive performance and postmortem...
Rachel Bercovitch

Age-related differences in memory encoding as a function of pupillary dynamics

2 weeks ago
Pupillary dynamics are known to depend on tonic and phasic activity of the brainstem locus coeruleus (LC), a key neuromodulatory nucleus. The LC shows a decline in its structural integrity in older age that likely impacts long-term memory. While several studies have explored the link between pupil dilation and successful memory encoding, little is known about the effects of aging on this relationship. This study investigated pupil dynamics in young and older adults during a rapid categorization...
Adrian Ruiz Chiapello

Psychological research on Alzheimer's disease in Pakistan: A systematic review of current trends and research gaps

2 weeks ago
Alzheimer's disease (AD) is an escalating public health concern in low- and middle-income countries like Pakistan, with rising prevalence among the aging population. While global research has increasingly addressed the psychological dimensions of AD, Pakistan's contribution remains limited. This systematic review, conducted in accordance with PRISMA guidelines, examines the scope and focus of psychological research on AD in Pakistan. Eleven empirical studies published between 2014 and 2025 were...
Amna Aurooj

Mitochondria-associated endoplasmic reticulum membranes as aging-sensitive signaling hubs in degenerative musculoskeletal diseases

2 weeks ago
Degenerative musculoskeletal diseases (DMDs), including osteoarthritis, osteoporosis, sarcopenia, and intervertebral disc degeneration, are highly prevalent age-related conditions characterized by progressive tissue dysfunction and loss of musculoskeletal integrity. Aging is accompanied by profound alterations in organelle homeostasis, metabolic signaling, and stress adaptation, among which mitochondria-endoplasmic reticulum communication has emerged as a critical regulatory axis....
Linbo Peng