Serum Metabolites Associate with Brain Amyloid Beta Deposition, Cognitive Dysfunction, and Alzheimers Disease Progression

Nho, K.; Kueider-Paisley, A.; Arnold, M.; MahmoudianDehkordi, S.; Risacher, S. L.; Louie, G.; Blach, C.; Baillie, R.; Han, X.; Kastenmüller, G.; Doraiswamy, P. M.; Kaddurah-Daouk, R.; Saykin, A. J.; Alzheimer's Disease Neuroimaging Initiative,; Alzheimer's Disease Metabolomics Consortium,

doi:10.1101/2020.11.25.394262

bioRxiv · 10.1101/2020.11.25.394262

Serum Metabolites Associate with Brain Amyloid Beta Deposition, Cognitive Dysfunction, and Alzheimers Disease Progression

Nho, K.·Kueider-Paisley, A.·Arnold, M.·MahmoudianDehkordi, S.·Risacher, S. L.·Louie, G.·Blach, C.·Baillie, R.·Han, X.·Kastenmüller, G.·Doraiswamy, P. M.·Kaddurah-Daouk, R.·Saykin, A. J.·Alzheimer's Disease Neuroimaging Initiative,·Alzheimer's Disease Metabolomics Consortium,

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Abstract

RATIONALEMetabolomics 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. OBJECTIVESWe examined 140 serum metabolites and their associations with brain amyloid-{beta} deposition, cognition, and conversion from mild cognitive impairment (MCI) to AD. FINDINGSSerum-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. CONCLUSIONPerturbations 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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Nho, K., Kueider-Paisley, A., Arnold, M., MahmoudianDehkordi, S., Risacher, S. L., Louie, G., Blach, C., Baillie, R., Han, X., Kastenmüller, G., Doraiswamy, P. M., Kaddurah-Daouk, R., Saykin, A. J., Alzheimer's Disease Neuroimaging Initiative,, Alzheimer's Disease Metabolomics Consortium,. 2020-11-27. Serum Metabolites Associate with Brain Amyloid Beta Deposition, Cognitive Dysfunction, and Alzheimers Disease Progression. https://doi.org/10.1101/2020.11.25.394262

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