期刊
MOLECULAR PSYCHIATRY
卷 27, 期 11, 页码 4800-4808出版社
SPRINGERNATURE
DOI: 10.1038/s41380-022-01729-x
关键词
-
资金
- Sao Paulo Research Foundation [06/55318-1, 09/09134-4, 13/08028-1, 14/50931-3 16/24326-0, 18/16626-0]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [466763/2014-0, 465355/2014-5, 403502/2020-9]
- Alzheimer Association
- National Institute of Health [K24AG053435]
- FAPEMIG [00314-16]
- NIH [R01AG17917]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [06/55318-1] Funding Source: FAPESP
Dementia is more common in Blacks than in Whites, possibly due to a combination of environmental and biological factors. Interestingly, studies have shown a lower risk of dementia associated with APOE epsilon 4 in individuals of African ancestry. However, the underlying biological factors are not well understood. This study found that African ancestry was associated with a lower burden of neuropathology, but in individuals with severe neuropathology, it was associated with worse clinical symptoms of dementia.
Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE epsilon 4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE epsilon 4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE epsilon 4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE epsilon 4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE epsilon 4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE epsilon 4 risk compared to European ancestry.
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