Abstract
Accumulating evidence suggests that BMI1 confers protective effects against Alzheimer's disease (AD). However, the mechanism remains elusive. Given recent pathophysiological evidence, we investigated whether genetic variants in BMI1 is associated with AD biomarkers. We used genetic and AD biomarker data from two independent well-characterized cohorts: Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). First, we performed a gene-based association analysis of single-nucleotide polymorphisms (SNPs) in BMI1 with cerebrospinal fluid (CSF) Aβ1-42 levels. Second, we performed longitudinal association analyses of SNPs with cognitive decline rates using linear mixed-effects models. Gene-based genetic association analysis identified SNPs in BMI1 as being significantly associated with CSF Aβ1-42 levels after adjusting for multiple testing using permutation. Participants with minor alleles of BMI1 rs17415557 with the most significant association have increased CSF Aβ1-42 levels, which was interestingly prominent within amyloid-positive participants. Further analysis identified and replicated the minor allele of rs17415557 as being significantly associated with slower cognitive decline rates in AD. Our findings provide fundamental evidence that BMI1 rs17415557 may serve as a protective mechanism related to AD pathogenesis, which supports the results of previous studies linking BMI1 to protection against AD.
Published Version
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