Dataset Information

APOE region molecular signatures of Alzheimer's disease across races/ethnicities.

ABSTRACT: The role of even the strongest genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) ?4 allele, in its etiology remains poorly understood. We examined molecular signatures of AD defined as differences in linkage disequilibrium patterns between AD-affected and -unaffected whites (2673/16,246), Hispanics (392/867), and African Americans (285/1789), separately. We focused on 29 polymorphisms from 5 genes in the APOE region emphasizing beneficial and adverse effects of the APOE ?2- and ?4-coding single-nucleotide polymorphisms, respectively, and the differences in the linkage disequilibrium structures involving these alleles between AD-affected and -unaffected subjects. Susceptibility to AD is likely the result of complex interactions of the ?2 and ?4 alleles with other polymorphisms in the APOE region, and these interactions differ across races/ethnicities corroborating differences in the adverse and beneficial effects of the ?4 and ?2 alleles. Our findings support complex race/ethnicity-specific haplotypes promoting and protecting against AD in this region. They contribute to better understanding of polygenic and resilient mechanisms, which can explain why even homozygous ?4 carriers may not develop AD.

SUBMITTER: Kulminski AM

PROVIDER: S-EPMC7064423 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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APOE region molecular signatures of Alzheimer's disease across races/ethnicities.

Kulminski Alexander M AM Shu Leonardo L Loika Yury Y Nazarian Alireza A Arbeev Konstantin K Ukraintseva Svetlana S Yashin Anatoliy A Culminskaya Irina I

Neurobiology of aging 20191111

The role of even the strongest genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) ε4 allele, in its etiology remains poorly understood. We examined molecular signatures of AD defined as differences in linkage disequilibrium patterns between AD-affected and -unaffected whites (2673/16,246), Hispanics (392/867), and African Americans (285/1789), separately. We focused on 29 polymorphisms from 5 genes in the APOE region emphasizing beneficial and adverse effects of the AP ...[more]

PMID: 31813627

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Dataset Information

APOE region molecular signatures of Alzheimer's disease across races/ethnicities.

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APOE region molecular signatures of Alzheimer's disease across races/ethnicities.

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