APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia.
PLoS Biol
; 20(12): e3001863, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36512526
ABSTRACT
Alzheimer's disease is marked by intracellular tau aggregates in the medial temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we examined codependent structural variations between the MTL's most vulnerable structure, the hippocampus (HC), and the DN at subregion resolution in individuals with Alzheimer's disease and related dementia (ADRD). By leveraging the power of the approximately 40,000 participants of the UK Biobank cohort, we assessed impacts from the protective APOE É2 and the deleterious APOE É4 Alzheimer's disease alleles on these structural relationships. We demonstrate É2 and É4 genotype effects on the inter-individual expression of HC-DN co-variation structural patterns at the population level. Across these HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix's fimbria, and their cortical partners related to ADRD risk. Analyses of the rich phenotypic profiles in the UK Biobank cohort further revealed male-specific HC-DN associations with air pollution and female-specific associations with cardiovascular traits. We also showed that APOE É2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our structural, genetic, and phenotypic analyses in this large epidemiological cohort reinvigorate the often-neglected interplay between APOE É2 dosage and sex and link APOE alleles to inter-individual brain structural differences indicative of ADRD familial risk.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Encéfalo
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Caracteres Sexuais
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Doença de Alzheimer
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article