Tau pathway-based gene analysis on PET identifies CLU and FYN in a Korean cohort

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-12-03 DOI:10.1002/alz.14416

Dahyun Yi, Min Soo Byun, Jong-Ho Park, Jong-Won Kim, Gijung Jung, Hyejin Ahn, Jun-Young Lee, Yun-Sang Lee, Yu Kyeong Kim, Koung Mi Kang, Chul-Ho Sohn, Shiwei Liu, Yen-Ning Huang, Andrew J. Saykin, Dong Young Lee, Kwangsik Nho, for the KBASE research group

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Abstract

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.

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基于Tau通路的PET基因分析鉴定了韩国队列中的CLU和FYN

遗传变异对tau蛋白聚集的影响，是阿尔茨海默病（AD）的一个关键因素，仍未完全了解。我们的目的是在韩国队列中使用基于通路的候选基因关联分析来识别与脑tau沉积相关的新基因。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.