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Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression.

Publication ,  Journal Article
Nho, K; Kueider-Paisley, A; Arnold, M; MahmoudianDehkordi, S; Risacher, SL; Louie, G; Blach, C; Baillie, R; Han, X; Kastenmüller, G; Saykin, AJ ...
Published in: Brain Commun
2021

Metabolomics in the Alzheimer's Disease Neuroimaging Initiative cohort provides a powerful tool for mapping biochemical changes in Alzheimer's disease, and a unique opportunity to learn about the association between circulating blood metabolites and brain amyloid-β deposition in Alzheimer's disease. We examined 140 serum metabolites and their associations with brain amyloid-β deposition, cognition and conversion from mild cognitive impairment to Alzheimer's disease in the Alzheimer's Disease Neuroimaging Initiative. Processed [18F] Florbetapir PET images were used to perform a voxel-wise statistical analysis of the effect of metabolite levels on amyloid-β accumulation across the whole brain. We performed a multivariable regression analysis using age, sex, body mass index, apolipoprotein E ε4 status and study phase as covariates. We identified nine metabolites as significantly associated with amyloid-β deposition after multiple comparison correction. Higher levels of one acylcarnitine (C3; propionylcarnitine) and one biogenic amine (kynurenine) were associated with decreased amyloid-β accumulation and higher memory scores. However, higher levels of seven phosphatidylcholines (lysoPC a C18:2, PC aa C42:0, PC ae C42:3, PC ae C44:3, PC ae C44:4, PC ae C44:5 and PC ae C44:6) were associated with increased brain amyloid-β deposition. In addition, higher levels of PC ae C44:4 were significantly associated with lower memory and executive function scores and conversion from mild cognitive impairment to Alzheimer's disease dementia. Our findings suggest that dysregulation of peripheral phosphatidylcholine metabolism is associated with earlier pathological changes noted in Alzheimer's disease as measured by brain amyloid-β deposition as well as later clinical features including changes in memory and executive functioning. Perturbations in phosphatidylcholine metabolism may point to issues with membrane restructuring leading to the accumulation of amyloid-β in the brain. Additional studies are needed to explore whether these metabolites play a causal role in the pathogenesis of Alzheimer's disease or if they are biomarkers for systemic changes during preclinical phases of the disease.

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Published In

Brain Commun

DOI

EISSN

2632-1297

Publication Date

2021

Volume

3

Issue

3

Start / End Page

fcab139

Location

England

Related Subject Headings

  • 5202 Biological psychology
  • 3209 Neurosciences
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nho, K., Kueider-Paisley, A., Arnold, M., MahmoudianDehkordi, S., Risacher, S. L., Louie, G., … Alzheimer’s Disease Neuroimaging Initiative and on behalf of the Alzheimer Disease Metabolomics Consortium, . (2021). Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression. Brain Commun, 3(3), fcab139. https://doi.org/10.1093/braincomms/fcab139
Nho, Kwangsik, Alexandra Kueider-Paisley, Matthias Arnold, Siamak MahmoudianDehkordi, Shannon L. Risacher, Gregory Louie, Colette Blach, et al. “Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression.Brain Commun 3, no. 3 (2021): fcab139. https://doi.org/10.1093/braincomms/fcab139.
Nho K, Kueider-Paisley A, Arnold M, MahmoudianDehkordi S, Risacher SL, Louie G, et al. Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression. Brain Commun. 2021;3(3):fcab139.
Nho, Kwangsik, et al. “Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression.Brain Commun, vol. 3, no. 3, 2021, p. fcab139. Pubmed, doi:10.1093/braincomms/fcab139.
Nho K, Kueider-Paisley A, Arnold M, MahmoudianDehkordi S, Risacher SL, Louie G, Blach C, Baillie R, Han X, Kastenmüller G, Doraiswamy PM, Kaddurah-Daouk R, Saykin AJ, Alzheimer’s Disease Neuroimaging Initiative and on behalf of the Alzheimer Disease Metabolomics Consortium. Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression. Brain Commun. 2021;3(3):fcab139.

Published In

Brain Commun

DOI

EISSN

2632-1297

Publication Date

2021

Volume

3

Issue

3

Start / End Page

fcab139

Location

England

Related Subject Headings

  • 5202 Biological psychology
  • 3209 Neurosciences
  • 3202 Clinical sciences