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HLA is a potent immunoinflammatory target in asymptomatic Alzheimer's disease

11 months 2 weeks ago
Alzheimer's disease (AD) is a common neurodegenerative disease, neuroinflammation is an early pathological feature of AD. However, the alteration of the immune microenvironment in asymptomatic AD was not fully explained. In this study, we aimed to utilize the transcriptome data of AD patients in public databases to reveal the change of immune microenvironment in asymptomatic AD and screen the potential drug targets. A series of bioinformatics analyses were done, including differentially...
Yingwei Zheng

Whole-genome sequencing to identify rare variants in East Asian patients with dementia with Lewy bodies

11 months 2 weeks ago
Dementia with Lewy bodies (DLB) is the second most common form of age-related dementia, following Alzheimer's disease (AD). DLB is associated with a worse prognosis than AD and is characterized by a more rapid progression of cognitive impairment and a poorer quality of life. In addition, the pathogenesis of DLB is less understood than that of AD, and only three genes-SNCA (α-synuclein), APOE (apolipoprotein E), and GBA1 (glucosylceramidase beta 1)-have been convincingly demonstrated to be...
Tetsuaki Kimura

Exome sequencing in Asian populations identifies low-frequency and rare coding variation influencing Parkinson's disease risk

11 months 2 weeks ago
Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in...
Elaine Gy Chew

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease

11 months 2 weeks ago
The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron...
Stephanie L Fowler

Diets to promote healthy brain ageing

11 months 2 weeks ago
Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical...
Sokratis Charisis

Cross-sectional and longitudinal relationships among blood-brain barrier disruption, Alzheimer's disease biomarkers, and cognition in cognitively normal older adults

11 months 2 weeks ago
Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer's disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships...
Marisa Denkinger

Age-Related Hearing Loss: A cross-sectional study of healthy older Australians

11 months 2 weeks ago
Introduction Hearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing...
Carlene J Britt

Nutrient control of growth and metabolism through mTORC1 regulation of mRNA splicing

11 months 2 weeks ago
Cellular growth and organismal development are remarkably complex processes that require the nutrient-responsive kinase mechanistic target of rapamycin complex 1 (mTORC1). Anticipating that important mTORC1 functions remained to be identified, we employed genetic and bioinformatic screening in C. elegans to uncover mechanisms of mTORC1 action. Here, we show that during larval growth, nutrients induce an extensive reprogramming of gene expression and alternative mRNA splicing by acting through...
Takafumi Ogawa