Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function.

ABSTRACT: Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) have a substantial genetic basis, with APOE4 homozygotes increasingly recognized as a distinct genetic subtype. To identify genotype-specific metabolic pathways and modifiable risk factors, we integrated genetic, plasma metabolomic and dietary data from 4,215 women and 1,490 men in prospective cohorts. Here we show that the associations of 57 metabolites with dementia risk varied by APOE4 genotype or other AD/ADRD risk variants. For example, cholesteryl esters and sphingomyelins were most strongly associated with increased dementia risk in APOE4 homozygotes, whereas inverse associations with glycerides were specific to this genotype. Dimethylguanidino-valeric acid was more strongly associated with dementia risk among carriers of t

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12618253 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature