Basic Science and Pathogenesis

Large-scale genome-wide association studies (GWAS) of Alzheimer's disease (AD) from European ancestry identified many genetic variants associated with clinical diagnosis of AD dementia. However, it remains unclear whether these AD-related variants are associated with AD biomarkers, particularly...

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Bibliographic Details
Published in:Alzheimer's & dementia 2024-12, Vol.20 Suppl 1, p.e092461
Main Authors: Ahn, Hyejin, Byun, Min Soo, Yi, Dahyun, Jung, Gijung, Huang, Yen-Ning, Risacher, Shannon L, Griswold, Anthony J, Pericak-Vance, Margaret A, Kim, Yu Kyeong, Lee, Yun-Sang, Sohn, Chul-Ho, Kang, Koung Mi, Lee, Jun-Young, Saykin, Andrew J, Nho, Kwangsik, Lee, Dong Young
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Atrophy - pathology
Cognitive Dysfunction - genetics
Cognitive Dysfunction - pathology
Female
Genome-Wide Association Study
Hippocampus - diagnostic imaging
Hippocampus - pathology
Humans
Magnetic Resonance Imaging
Male
Polymorphism, Single Nucleotide - genetics
Positron-Emission Tomography
Republic of Korea
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Summary:Large-scale genome-wide association studies (GWAS) of Alzheimer's disease (AD) from European ancestry identified many genetic variants associated with clinical diagnosis of AD dementia. However, it remains unclear whether these AD-related variants are associated with AD biomarkers, particularly hippocampal atrophy, a well-known neurodegeneration biomarker of AD in a Korean population. In this study, we investigated the association between known AD risk single nucleotide polymorphisms (SNPs) and hippocampal atrophy along the AD continuum in older Korean adults. A total of 487 participants (258 cognitively normal olde adults [CN], 144 mild cognitive impairment [MCI], 85 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) were included for analysis. All participants underwent C-PiB-PET/MRI. Hippocampal volume adjusted for intracranial volume (HVa) was obtained from 3D T1-weighted MRI scans using FreeSurfer and used as a neurodegeneration marker of AD. Global beta-amyloid (Aβ) deposition was calculated from PiB uptake in the global cortical region-of-interest using SPM12. From the genetic evidence gathered by the AD Sequencing Project (ADSP), which consists of 76 SNPs associated with AD, we selected 38 SNPs with a minor allele frequency (MAF) greater than 1% from the genotyping data imputed using the TOPMed imputation server in the KBASE cohort. Among 38 known AD-related SNPs, three SNPs (rs6966331 in EPDR1, rs2242595 in MYO15A, and rs17125924 in FERMT2) were associated with HVa in an initial exploratory analysis (p
ISSN:1552-5279
1552-5279
DOI:10.1002/alz.092461