Abstract RATIONALE Metabolomics in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort provides a powerful tool for mapping biochemical changes in AD, and a unique opportunity to learn about the association between circulating blood metabolites and brain amyloid-β deposition in AD. OBJECTIVES We examined 140 serum metabolites and their associations with brain amyloid-β deposition, cognition, and conversion from mild cognitive impairment (MCI) to AD. FINDINGS Serum-based targeted metabolite levels were measured in 1,531 ADNI participants. We performed association analysis of metabolites with brain amyloid-β deposition measured from [18F] Florbetapir PET scans. We identified nine metabolites as significantly associated with amyloid-β deposition after FDR-based multiple comparison correction. Higher levels of one acylcarnitine (C3; propionylcarnitine) and one biogenic amine (kynurenine) were associated with decreased amyloid-β accumulation. However, higher levels of seven phosphatidylcholines (PC) were associated with increased amyloid deposition. In addition, PC ae C44:4 was significantly associated with cognition and conversion from MCI to AD dementia. CONCLUSION Perturbations in PC and acylcarnitine metabolism may play a role in features intrinsic to AD including amyloid-β deposition and cognitive performance.

Serum Metabolites Associated with Brain Amyloid Beta Deposition, Cognitive Dysfunction, and Alzheimer’s Disease Progression