ArticleBrain, behavior, and immunity2024
Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.
Article in Brain, behavior, and immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- The interplay of air pollution with plasma neurodegenerative markers and metabolome for dementia, Parkinson's disease and all-cause mortality risks and transitions: The UK Biobank study.Ecotoxicology and environmental safety · 2026Article
- Life's crucial 9, plasma proteomics, and the risk of major complications and mortality in MASLD.npj metabolic health and disease · 2026Article
- Associations of cardiovascular health and genetic susceptibility with incident psoriatic arthritis: findings from two cohort studies.Clinical rheumatology · 2026Article
- Psychosocial adversity captured by ICD-10 Z-codes and mortality risk: evidence from the UK Biobank.GeroScience · 2026Article
- Insomnia, proteomic characteristics, and mortality risk in depression: a UK Biobank study.BMC psychiatry · 2026Article
- UK Biobank at 20 - a growing, global resource for dementia research.Nature reviews. Neurology · 2026Review
- Plasma proteomics link menopause timing to brain aging and dementia risk.Research square · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026Article
- Multiomics: the intersection of personalized nutrition in cardiometabolic diseases.Journal of translational medicine · 2026Review
- Machine learning integration of bulk and single-cell RNA-Seq data reveals COPS2 as a central immune regulator in deep vein thrombosis.American journal of translational research · 2026Article
- Pre-diagnostic plasma proteomics profile uncovers new biomarkers and mechanistic insights for incident kidney cancer.International journal of surgery (London, England) · 2026Article
- Microbiota-host crosstalk: the role of short-term dietary restriction in neurological and metabolic dysregulation.NPJ biofilms and microbiomes · 2025Article
- Socio-environmental and health-related factors and their association with longitudinal change in brain neuroimaging markers through the plasma metabolome among UK adults: An additive Bayesian network analysis.Brain, behavior, & immunity - health · 2025Article
- Allostatic load and kidney cancer incidence and mortality: a genetic susceptibility and proteomic mediation analysis.BMC cancer · 2025Article
- Profiling 92 circulating neurobiological proteins identifies novel candidate biomarkers of long-term cognitive outcome after ischemic stroke.Scientific reports · 2025Article
- Cardiovascular health and its association with dementia, Parkinson's Disease, and mortality among UK older adults.Brain, behavior, & immunity - health · 2025Article
- Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study.Molecular psychiatry · 2025Article
- Integrated pan-cancer analysis of ADM's role in prognosis, immune modulation and resistance.Frontiers in immunology · 2025Article
- Proteomic Biomarkers as Mediators in the Association Between Air Pollution and Incident Depression and Anxiety: Evidence From the UK Biobank.Depression and anxiety · 2025Article
- Plasma proteomics for risk prediction of Alzheimer's disease in the general population.Aging cell · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundThe study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk.
methodsThe present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006-2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life's Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into "mediation only" or pure indirect effect (PIE), "interaction only" or interaction referent (INTREF), "neither mediation nor interaction" or controlled direct effect (CDE), and "both mediation and interaction" or mediated interaction (INTMED).
resultsThe study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03-1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730).
conclusionDementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained ∼ 54 % of the total effect.
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