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• W3202168364 abstract "Accumulating evidence suggests that BMI1 confers protective effects against Alzheimer's disease (AD). However, the mechanism remains elusive. Based on recent pathophysiological evidence, we sought for the first time to identify genetic variants in BMI1 as associated with AD biomarkers, including amyloid-β.We used genetic, longitudinal cognition, and cerebrospinal fluid (CSF) biomarker data from participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (N = 1565). First, we performed a gene-based association analysis of common single nucleotide polymorphisms (SNPs) (minor allele frequency (MAF) > 5%) located within ± 20 kb of the gene boundary of BMI1, an optimal width for including potential regulatory SNPs in the 5' and 3' untranslated regions (UTR) of BMI1, with CSF Aβ1-42 levels. Second, we performed cross-sectional and longitudinal association analyses of SNPs in BMI1 with cognitive performance using linear and mixed-effects models. We replicated association of SNPs in BMI1 with cognitive performance in an independent cohort (N=1084), Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP).Gene-based genetic association analysis showed that BMI1 was significantly associated with CSF Aβ1-42 levels after adjusting for multiple testing using permutation (permutation-corrected p value=0.005). rs17415557 in BMI1 showed the most significant association with CSF Aβ1-42 levels. Participants with minor alleles of rs17415557 have increased CSF Aβ1-42 levels compared to those with no minor alleles. 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." @default.
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• W3202168364 date "2021-10-05" @default.
• W3202168364 modified "2023-10-14" @default.
• W3202168364 title "BMI1 is associated with CSF amyloid-β and rates of cognitive decline in Alzheimer’s disease" @default.
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• W3202168364 doi "https://doi.org/10.1186/s13195-021-00906-4" @default.
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