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

TitleAPOE region molecular signatures of Alzheimer's disease across races/ethnicities.
Publication TypeJournal Article
Year of Publication2020
AuthorsKulminski, AM, Shu, L, Loika, Y, Nazarian, A, Arbeev, KG, Ukraintseva, S, Yashin, A, Culminskaya, I
JournalNeurobiol Aging
Volume87
Pagination141.e1-141.e8
Date Published2020 03
ISSN Number1558-1497
KeywordsAlleles, Alzheimer disease, Apolipoproteins E, Continental Population Groups, Haplotypes, Heterozygote, Homozygote, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Risk Factors
Abstract

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 APOE ε2- and ε4-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 ε2 and ε4 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 ε4 and ε2 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 ε4 carriers may not develop AD.

DOI10.1016/j.neurobiolaging.2019.11.007
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/31813627?dopt=Abstract

Alternate JournalNeurobiol Aging
Citation Key11320
PubMed ID31813627
PubMed Central IDPMC7064423
Grant ListHHSN268201500001C / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
R01 AG047310 / AG / NIA NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
RC4 AG039029 / AG / NIA NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
P30 AG034424 / AG / NIA NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
P01 AG043352 / AG / NIA NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 AG061853 / AG / NIA NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States