Differences in plasma metabolites related to Alzheimer’s disease, APOE ε4 status, and ethnicity

INTRODUCTION: We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer’s disease (AD).
METHODS: Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH), and non-Hispanic white (NHW) ancestry using untargeted liquid-chromatography-based ultra-high-resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and apolipoprotein E gene (APOE) ε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD-associated metabolites.
RESULTS: A total of 5929 annotated metabolites were measured. Partial least squares discriminant analysis (PLS-DA) inferred that AD clustered separately from healthy controls (area under the curve [AUC] = 0.9816); discriminating pathways included glycerophospholipid, sphingolipid, and non-essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC = 0.9275), and differed between APOE ε4 carriers and non-carriers (AUC = 0.9972).
DISCUSSION: Metabolites, specifically lipids, were associated with AD, APOE ε4, and ethnic group. Metabolite profiling can identify perturbed AD pathways, but genetic and ancestral background need to be considered.