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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵† Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abbreviations: AD: Alzheimer’s disease; ADMC: Alzheimer’s Disease Metabolomics Consortium; ADNI: Alzheimer’s Disease Neuroimaging Initiative; APOE: apolipoprotein E; EMCI: Early mild cognitive impairment; FDR: False discovery rate; LMCI: Late mild cognitive impairment; MCI: Mild cognitive impairment; PC: phosphatidylcholine; PET: positron emission tomography; SM: sphingomyelin; SMC: subjective memory complaint