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
Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, South Korea.
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
Alzheimers Dement. 2025 Feb;21(2):e14416. doi: 10.1002/alz.14416. Epub 2024 Dec 3.
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.
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 F-AV-1451 positron emission tomography (PET) scans, with additional voxel-wise analysis conducted using Statistical Parametric Mapping 12 (SPM12).
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.
CLU and FYN may play specific roles in tau pathophysiology, offering potential targets for biomarkers and therapies.
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.
基因变异对tau蛋白聚集的影响尚未完全明确，而tau蛋白聚集是阿尔茨海默病（AD）的关键因素。我们旨在通过基于通路的候选基因关联分析，在韩国队列中识别与脑tau沉积相关的新基因。
我们分析了来自成熟的韩国AD连续队列（韩国阿尔茨海默病早期诊断和预测脑老化研究；KBASE）的146名老年人的数据。选择了15个与tau通路和AD相关的候选基因。使用PLINK（全基因组关联和基于人群连锁分析的工具集）对通过F-AV-1451正电子发射断层扫描（PET）测量的tau沉积进行关联分析，并使用统计参数映射12（SPM12）进行额外的体素级分析。
CLU和FYN与tau沉积显著相关，最显著的单核苷酸多态性（SNP）分别为rs149413552和rs57650567。这些SNP与关键脑区tau增加有关，并与载脂蛋白E（APOE）ε4显示出加性效应。
CLU和FYN可能在tau病理生理学中发挥特定作用，为生物标志物和治疗提供潜在靶点。
基于基因的分析确定CLU和FYN与正电子发射断层扫描（PET）上的tau沉积相关。CLU rs149413552和FYN rs57650567与脑tau沉积相关。rs149413552和rs57650567与脑结构萎缩相关。CLU rs149413552与即时言语记忆相关。CLU和FYN可能在tau病理生理学中发挥特定作用。
