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Alzheimers. Dement., Dec 03 2024, | https://doi.org/10.1002/alz.14416
Tau pathway-based gene analysis on PET identifies CLU and FYN in a Korean cohort
Dahyun Yi1, Min Soo Byun2,3, Jong-Ho Park4, Jong-Won Kim5, Gijung Jung1, Hyejin Ahn6, Jun-Young Lee7, Yun-Sang Lee8, Yu Kyeong Kim9, Koung Mi Kang10,11, Chul-Ho Sohn10, Shiwei Liu12,13, Yen-Ning Huang12,13, Andrew J. Saykin12,13, Dong Young Lee1,2,3, Kwangsik Nho12,13 for the KBASEresearch group
1 Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, South Korea
2 Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea
3 Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
4 Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea
5 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea
6 Interdisciplinary Program of Cognitive Science, Seoul National University College of Humanities, Gwanak-gu, Seoul, South Korea
7 Department of Psychiatry, Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, South Korea
8 Department of Nuclear Medicine, Seoul National University College of Medicine, Jongro-gu, Seoul, South Korea
9 Department of Nuclear Medicine, Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, South Korea
10 Department of Radiology, Seoul National University Hospital, Jongro-gu, Seoul, South Korea
11 Department of Radiology, Seoul National University College of Medicine, Jongro-gu, Seoul, South Korea
12 Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
13 Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
Andrew J. Saykin, Dong Young Lee, andKwangsik Nho are co-corresponding authors.
Correspondence: Kwangsik Nho, Andrew J. Saykin, Dong Young Lee
1 Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, South Korea
2 Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea
3 Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
4 Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea
5 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea
6 Interdisciplinary Program of Cognitive Science, Seoul National University College of Humanities, Gwanak-gu, Seoul, South Korea
7 Department of Psychiatry, Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, South Korea
8 Department of Nuclear Medicine, Seoul National University College of Medicine, Jongro-gu, Seoul, South Korea
9 Department of Nuclear Medicine, Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, South Korea
10 Department of Radiology, Seoul National University Hospital, Jongro-gu, Seoul, South Korea
11 Department of Radiology, Seoul National University College of Medicine, Jongro-gu, Seoul, South Korea
12 Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
13 Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
Andrew J. Saykin, Dong Young Lee, andKwangsik Nho are co-corresponding authors.
Correspondence: Kwangsik Nho, Andrew J. Saykin, Dong Young Lee
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.
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.
논문정보
- Research article
- 2024년 12월 (BRIC 등록일 2024-12-06)
- 국내(교신)+국외 연구진
- 생명과학 > 유전학
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