Interplay between age, APOE Ɛ4 and the metabolome in plasma and brain in Alzheimer's disease.

ABSTRACT: Age and the ε4 variant of the apolipoprotein E gene (APOE ε4) are two major drivers of Alzheimer's disease (AD). APOE is also the major determinant of longevity. How age and APOE interact in the development of AD is largely unknown. In this study we integrate metabolomics (N = 274,259) and proteomics (N = 54,219) data in plasma from the UK Biobank with the metabolomics (N = 514) and proteomics (N = 618) data in brain from the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) to understand the interplay of age, APOE ε4 and metabolome in the development of AD. We find that levels of β-hydroxybutyrate (BHBA) and branch-chained amino acids (BCAAs) are dysregulated in plasma and brains of AD patients. APOE ε4 carriers manifest significantly higher plasma concentration of BHB

SUBMITTER: Amin N 

PROVIDER: S-EPMC12578868 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature