Hospital-treated prevalent infections, the plasma proteome and incident dementia among UK older adults

The plasma proteome can mediate the association of hospital-treated infections with dementia incidence. We screened up to 37,269 UK Biobank participants aged 50–74 years for the presence of a prevalent hospital-treated infection, subsequently tested as a predictor for ≤1,463 plasma proteins and deme...

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Published in:iScience Vol. 26; no. 12; p. 108526
Main Authors: Beydoun, May A., Beydoun, Hind A., Noren Hooten, Nicole, Meirelles, Osorio, Li, Zhiguang, El-Hajj, Ziad W., Weiss, Jordan, Maino Vieytes, Christian A., Launer, Lenore J., Evans, Michele K., Zonderman, Alan B.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 15.12.2023
Elsevier
Subjects:
Microbiome
Neurology
Public health
Neurology
Public health
Microbiome
ISSN:2589-0042, 2589-0042
Online Access:Get full text
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Summary:The plasma proteome can mediate the association of hospital-treated infections with dementia incidence. We screened up to 37,269 UK Biobank participants aged 50–74 years for the presence of a prevalent hospital-treated infection, subsequently tested as a predictor for ≤1,463 plasma proteins and dementia incidence. Four-way decomposition models decomposed infection-dementia total effect into pure mediation, pure interaction, neither or both through the plasma proteome. Hospital-treated infections increased dementia two-fold. The strongest mediation effect was through the growth differentiation factor 15 (GDF15) protein. Top 17 proteomic mediators explained collectively 5% of the total effect, while pathway analysis of all mediators (k = 221 plasma proteins) revealed top pathways including the immune system, signal transduction, metabolism, disease and metabolism of proteins, with the GDF15 cluster reflecting most strongly the “transmembrane receptor protein tyrosine kinase signaling pathway”. The association of hospital-treated infections with dementia was partially mediated through GDF15 and other plasma proteomic markers. [Display omitted] •Up to 37,269 UK Biobank participants (50+ years) had plasma proteomic data•Hospital-treated infections were associated with two-folds increased dementia risk•Growth differentiation factor 15 (GDF15) protein was the strongest mediator Neurology; Public health; Microbiome
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.108526