Genetic overlap between Alzheimer's disease and blood lipid levels.
Neurobiol Aging
; 108: 189-195, 2021 12.
Article
in En
| MEDLINE
| ID: mdl-34340865
ABSTRACT
Late-onset Alzheimer's disease (AD) has a significant genetic component, but the molecular mechanisms through which genetic risk factors contribute to AD pathogenesis are unclear. We screened for genetic sharing between AD and the blood levels of 615 metabolites to elucidate how the polygenic architecture of AD affects metabolomic profiles. We retrieved summary statistics from genome-wide association studies of AD and the metabolite blood levels and assessed for shared genetic etiology, using a polygenic risk score-based approach. For the blood levels of 31 metabolites, all of which were lipids, we identified and replicated genetic sharing with AD. We also found a positive genetic concordance - implying that genetic risk factors for AD are associated with higher blood levels - for 16 of the 31 replicated metabolites. In the brain, lipids and their intermediate metabolites have essential structural and functional roles, such as forming and dynamically regulating synaptic membranes. Our results imply that genetic risk factors for AD affect lipid levels, which may be leveraged to develop novel treatment strategies for AD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Multifactorial Inheritance
/
Genome-Wide Association Study
/
Alzheimer Disease
/
Lipids
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
Neurobiol Aging
Year:
2021
Type:
Article
Affiliation country:
Netherlands