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

1 year 1 month 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

1 year 1 month 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

1 year 1 month 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

1 year 1 month 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