The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses.
Transl Psychiatry
; 14(1): 204, 2024 May 18.
Article
em En
| MEDLINE
| ID: mdl-38762535
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Imageamento por Ressonância Magnética
/
Proteoma
/
Análise da Randomização Mendeliana
/
Disfunção Cognitiva
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá