Abstract | Introduction: We previously reported genetic associations of the top Alzheimer's disease (AD) risk alleles with amyloid deposition and neurodegeneration. Here, we report the association of these variants with [ 18F]flortaucipir standardized uptake value ratio (SUVR). Methods: We analyzed the [ 18F]flortaucipir scans of 352 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 54 dementia (DEM) participants from Alzheimer's Disease Neuroimaging Initiative (ADNI)2 and 3. We ran step-wise regression with log-transformed [ 18F]flortaucipir meta-region of interest SUVR as the outcome measure and genetic variants, age, sex, and apolipoprotein E ( APOE) ε4 as predictors. The results were visualized using parametric mapping at familywise error cluster-level-corrected P < .05. Results:
APOE ε4 showed significant (P < .05) associations with tau deposition across all disease stages. Other significantly associated genes include variants in ABCA7 in CN, CR1 in MCI, BIN1 and CASS4 in MCI and dementia participants. Discussion: We found significant associations to tau deposition for ABCA7, BIN1, CASS4, and CR1, in addition to APOE ε4. These four variants have been previously associated with tau metabolism through model systems.
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Authors | Eddie Stage, Shannon L Risacher, Kathleen A Lane, Sujuan Gao, Kwangsik Nho, Andrew J Saykin, Liana G Apostolova, Alzheimer's Disease Neuroimaging Initiative |
Journal | Alzheimer's & dementia (Amsterdam, Netherlands)
(Alzheimers Dement (Amst))
Vol. 14
Issue 1
Pg. e12308
( 2022)
ISSN: 2352-8729 [Print] United States |
PMID | 35592828
(Publication Type: Journal Article)
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Copyright | © 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. |