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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.*

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

Brain Commun. 3:fcab139 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Alzheimer’s Disease ; Amyloid-β ; Cognition ; Metabolomics ; Phosphatidylcholine Metabolism
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 2632-1297
e-ISSN 2632-1297
Zeitschrift Brain communications
Quellenangaben Band: 3, Heft: 3, Seiten: , Artikelnummer: fcab139 Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503891-001
DOI 10.1093/braincomms/fcab139
PubMed ID 34396103
Erfassungsdatum 2021-09-01
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