Serum Metabolites Associate with Brain Amyloid Beta Deposition, Cognitive Dysfunction, and Alzheimers Disease Progression
By
Kwangsik Nho,
Alexandra Kueider-Paisley,
Matthias Arnold,
Siamak MahmoudianDehkordi,
Shannon L Risacher,
Gregory Louie,
Colette Blach,
Rebecca Baillie,
Xianlin Han,
Gabi Kastenmüller,
P. Murali Doraiswamy,
Rima Kaddurah-Daouk,
Andrew J Saykin,
Alzheimer's Disease Neuroimaging Initiative,
Alzheimer's Disease Metabolomics Consortium
Posted 27 Nov 2020
bioRxiv DOI: 10.1101/2020.11.25.394262
RATIONALE: Metabolomics in the Alzheimers 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-{beta} deposition in AD. OBJECTIVES: We examined 140 serum metabolites and their associations with brain amyloid-{beta} 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-{beta} deposition measured from [18F] Florbetapir PET scans. We identified nine metabolites as significantly associated with amyloid-{beta} deposition after FDR-based multiple comparison correction. Higher levels of one acylcarnitine (C3; propionylcarnitine) and one biogenic amine (kynurenine) were associated with decreased amyloid-{beta} 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-{beta} deposition and cognitive performance.
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