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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This post is Copyright: 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 | December 3, 2024