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BMI1 is associated with CS8F amyloid-β and rates of cognitive decline in Alzheimer's disease.

TitleBMI1 is associated with CS8F amyloid-β and rates of cognitive decline in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2021
AuthorsKim JPyo, Kim B-H, Bice PJ, Seo SWon, Bennett DA, Saykin AJ, Nho K
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative
JournalAlzheimers Res Ther
Date Published2021 10 05
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Cognitive Dysfunction, Cross-Sectional Studies, Humans, Polycomb Repressive Complex 1, tau Proteins

BACKGROUND: 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.
METHODS: 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 Aβ 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).
RESULTS: Gene-based genetic association analysis showed that BMI1 was significantly associated with CSF Aβ levels after adjusting for multiple testing using permutation (permutation-corrected p value=0.005). rs17415557 in BMI1 showed the most significant association with CSF Aβ levels. Participants with minor alleles of rs17415557 have increased CSF Aβ 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.
CONCLUSIONS: 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.

Pubmed Link
Alternate JournalAlzheimers Res Ther
PubMed ID34610832
PubMed Central IDPMC8493672
Grant ListU01AG024904 / / Alzheimer's Disease Neuroimaging Initiative /
P50GM115318 / / National Institute of General Medicine Science /
/ / CIHR / Canada
R01 LM012535 / LM / NLM NIH HHS / United States
R03 AG063250 / AG / NIA NIH HHS / United States
P30 AG072976 / AG / NIA NIH HHS / United States
U01 AG068057 / AG / NIA NIH HHS / United States
U01 AG072177 / AG / NIA NIH HHS / United States
R01 LM013463 / LM / NLM NIH HHS / United States
P50 GM115318 / GM / NIGMS NIH HHS / United States

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