Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
Tau pathway-based gene analysis on PET identifies CLU and FYN in a Korean cohort.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yi Dahyun, Byun Min Soo, Park Jong-Ho, Kim Jong-Won, Jung Gijung, Ahn Hyejin, Lee Jun-Young, Lee Yun-Sang, Kim Yu Kyeong, Kang Koung Mi, Sohn Chul-Ho, Liu Shiwei, Huang Yen-Ning, Saykin Andrew J, Lee Dong Young, Nho Kwangsik, KBASE research group
Аннотация
INTRODUCTION: The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway-based candidate gene association analysis in a Korean cohort.
METHODS: We analyzed data for 146 older adults from the well-established Korean AD continuum cohort (Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease; KBASE). Fifteen candidate genes related to both tau pathways and AD were selected. Association analyses were performed using PLINK: A tool set for whole-genome association and population-based linkage analyses (PLINK) on tau deposition measured by 18F-AV-1451 positron emission tomography (PET) scans, with additional voxel-wise analysis conducted using Statistical Parametric Mapping 12 (SPM12).
RESULTS: CLU and FYN were significantly associated with tau deposition, with the most significant single-nucleotide polymorphisms (SNPs) being rs149413552 and rs57650567, respectively. These SNPs were linked to increased tau across key brain regions and showed additive effects with apolipoprotein E (APOE) ε4.
DISCUSSION: CLU and FYN may play specific roles in tau pathophysiology, offering potential targets for biomarkers and therapies.
HIGHLIGHTS: Gene-based analysis identified CLU and FYN as associated with tau deposition on positron emission tomography (PET). CLU rs149413552 and FYN rs57650567 were associated with brain tau deposition. rs149413552 and rs57650567 were associated with structural brain atrophy. CLU rs149413552 was associated with immediate verbal memory. CLU and FYN may play specific roles in tau pathophysiology.
METHODS: We analyzed data for 146 older adults from the well-established Korean AD continuum cohort (Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease; KBASE). Fifteen candidate genes related to both tau pathways and AD were selected. Association analyses were performed using PLINK: A tool set for whole-genome association and population-based linkage analyses (PLINK) on tau deposition measured by 18F-AV-1451 positron emission tomography (PET) scans, with additional voxel-wise analysis conducted using Statistical Parametric Mapping 12 (SPM12).
RESULTS: CLU and FYN were significantly associated with tau deposition, with the most significant single-nucleotide polymorphisms (SNPs) being rs149413552 and rs57650567, respectively. These SNPs were linked to increased tau across key brain regions and showed additive effects with apolipoprotein E (APOE) ε4.
DISCUSSION: CLU and FYN may play specific roles in tau pathophysiology, offering potential targets for biomarkers and therapies.
HIGHLIGHTS: Gene-based analysis identified CLU and FYN as associated with tau deposition on positron emission tomography (PET). CLU rs149413552 and FYN rs57650567 were associated with brain tau deposition. rs149413552 and rs57650567 were associated with structural brain atrophy. CLU rs149413552 was associated with immediate verbal memory. CLU and FYN may play specific roles in tau pathophysiology.