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We aimed to identify novel genes associated with brain tau deposition using pathway\u2010based candidate gene association analysis in a Korean cohort.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We analyzed data for 146 older adults from the well\u2010established 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\u2010genome association and population\u2010based linkage analyses\u00a0(PLINK) on tau deposition measured by\n 18<\/jats:sup>\n F\u2010AV\u20101451 positron emission tomography (PET) scans, with additional voxel\u2010wise analysis conducted using Statistical Parametric Mapping 12 (SPM12).\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n CLU<\/jats:italic>\n and\n FYN<\/jats:italic>\n were significantly associated with tau deposition, with the most significant single\u2010nucleotide 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 (\n APOE<\/jats:italic>\n ) \u03b54.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n CLU<\/jats:italic>\n and\n FYN<\/jats:italic>\n may play specific roles in tau pathophysiology, offering potential targets for biomarkers and therapies.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n Gene\u2010based analysis identified\n CLU<\/jats:italic>\n and\n FYN<\/jats:italic>\n as associated with tau deposition on positron emission tomography (PET).\n <\/jats:p>\n <\/jats:list-item>\n \n \n CLU<\/jats:italic>\n rs149413552 and\n FYN<\/jats:italic>\n rs57650567 were associated with brain tau deposition.\n <\/jats:p>\n <\/jats:list-item>\n \n rs149413552 and rs57650567 were associated with structural brain atrophy.<\/jats:p>\n <\/jats:list-item>\n \n \n CLU<\/jats:italic>\n rs149413552 was associated with immediate verbal memory.\n <\/jats:p>\n <\/jats:list-item>\n \n \n CLU<\/jats:italic>\n and\n FYN<\/jats:italic>\n may play specific roles in tau pathophysiology.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.14416","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T07:05:05Z","timestamp":1733209505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tau pathway\u2010based gene analysis on PET identifies\n CLU<\/i>\n and\n FYN<\/i>\n in a Korean cohort"],"prefix":"10.1002","volume":"21","author":[{"given":"Dahyun","family":"Yi","sequence":"first","affiliation":[{"name":"Institute of Human Behavioral Medicine Medical Research Center Seoul National University Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Soo","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Seoul National University Hospital Seoul South\u00a0Korea"},{"name":"Department of Psychiatry Seoul National University College of Medicine Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Precision Medicine Center Seoul National University Bundang Hospital Seongnam\u2010si Gyeonggi\u2010do South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics Samsung Medical Center Sungkyunkwan University School of Medicine Gangnam\u2010gu Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijung","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Human Behavioral Medicine Medical Research Center Seoul National University Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyejin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program of Cognitive Science Seoul National University College of Humanities Gwanak\u2010gu Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Seoul National University Boramae Medical Center, Dongjak\u2010gu Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Seoul National University College of Medicine Jongro\u2010gu Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Kyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Seoul National University Boramae Medical Center, Dongjak\u2010gu Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koung Mi","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul National University Hospital, Jongro\u2010gu Seoul South\u00a0Korea"},{"name":"Department of Radiology Seoul National University College of Medicine, Jongro\u2010gu Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul\u2010Ho","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul National University Hospital, Jongro\u2010gu Seoul South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Ning","family":"Huang","sequence":"additional","affiliation":[{"name":"Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Saykin","sequence":"additional","affiliation":[{"name":"Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Human 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