APOE region molecular signatures of Alzheimer's disease across races/ethnicities.
APOE polymorphism
Aging
Alzheimer's disease
Health span
Life span
Neurodegenerative disorders
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
21
12
2018
revised:
19
08
2019
accepted:
06
11
2019
pubmed:
10
12
2019
medline:
15
9
2020
entrez:
10
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31813627
pii: S0197-4580(19)30396-3
doi: 10.1016/j.neurobiolaging.2019.11.007
pmc: PMC7064423
mid: NIHMS1546006
pii:
doi:
Substances chimiques
ApoE protein, human
0
Apolipoproteins E
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
141.e1-141.e8Subventions
Organisme : NICHD NIH HHS
ID : R03 HD050374
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01 HC085085
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC65226
Pays : United States
Organisme : NIA NIH HHS
ID : RC2 AG036495
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG047310
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01 HC035129
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Organisme : NIA NIH HHS
ID : RC4 AG039029
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR033176
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG009740
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL080295
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200800007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01 HC015103
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL085251
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000124
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC55222
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG034424
Pays : United States
Organisme : NHLBI NIH HHS
ID : N02HL64278
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85086
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG008122
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01 HC085084
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG043352
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85082
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC75150
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85083
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC25195
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85079
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023629
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01 HC045133
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061853
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85080
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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