The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
18 May 2024
18 May 2024
Historique:
received:
18
09
2023
accepted:
23
04
2024
revised:
17
04
2024
medline:
19
5
2024
pubmed:
19
5
2024
entrez:
18
5
2024
Statut:
epublish
Résumé
Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins' plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8-19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.
Identifiants
pubmed: 38762535
doi: 10.1038/s41398-024-02915-x
pii: 10.1038/s41398-024-02915-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
204Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : G-18-0022359
Organisme : Heart and Stroke Foundation of Canada (Heart and Stroke Foundation)
ID : 399497
Organisme : Wellcome Trust (Wellcome)
ID : 108890/Z/15/Z
Organisme : Wellcome Trust (Wellcome)
ID : 204804/Z/16/Z
Organisme : Wellcome Trust (Wellcome)
ID : 104036/Z/14/Z
Organisme : Wellcome Trust (Wellcome)
ID : 220857/Z/20/Z
Organisme : Wellcome Trust (Wellcome)
ID : 216767/Z/19/Z
Organisme : Lister Institute of Preventive Medicine
ID : 173096
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_PC_17215
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/L023784/2
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/L023784/2
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_PC_17209
Informations de copyright
© 2024. The Author(s).
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