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Trares, K.* ; Bhardwaj, M.* ; Perna, L.* ; Stocker, H.R.* ; Petrera, A. ; Hauck, S.M. ; Beyreuther, K.* ; Brenner, H.* ; Schöttker, B.*

Association of the inflammation-related proteome with dementia development at older age: Results from a large, prospective, population-based cohort study.

Alzheimers Res. Ther. 14:128 (2022)

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BACKGROUND: Chronic inflammation is a central feature of several forms of dementia. However, few details on the associations of blood-based inflammation-related proteins with dementia incidence have been explored yet. METHODS: The Olink Target 96 Inflammation panel was measured in baseline serum samples (collected 07/2000-06/2002) of 1782 older adults from a German, population-based cohort study in a case-cohort design. Logistic regression models were used to assess the associations of biomarkers with all-cause dementia, Alzheimer's disease, and vascular dementia incidence. RESULTS: During 17 years of follow-up, 504 participants were diagnosed with dementia, including 163 Alzheimer's disease and 195 vascular dementia cases. After correction for multiple testing, 58 out of 72 tested (80.6%) biomarkers were statistically significantly associated with all-cause dementia, 22 with Alzheimer's disease, and 33 with vascular dementia incidence. We identified four biomarker clusters, among which the strongest representatives, CX3CL1, EN-RAGE, LAP TGF-beta-1, and VEGF-A, were significantly associated with dementia endpoints independently from other inflammation-related proteins. CX3CL1 (odds ratio [95% confidence interval] per 1 standard deviation increase: 1.41 [1.24-1.60]) and EN-RAGE (1.41 [1.25-1.60]) were associated with all-cause dementia incidence, EN-RAGE (1.51 [1.25-1.83]) and LAP TGF-beta-1 (1.46 [1.21-1.76]) with Alzheimer's disease incidence, and VEGF-A (1.43 [1.20-1.70]) with vascular dementia incidence. All named associations were stronger among APOE ε4-negative subjects. CONCLUSION: With this large, population-based cohort study, we show for the first time that the majority of inflammation-related proteins measured in blood samples are associated with total dementia incidence. Future studies should concentrate not only on single biomarkers but also on the complex relationships in biomarker clusters.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Alzheimer’s Disease ; Biomarker ; Cohort Study ; Dementia ; Inflammation ; Vascular Dementia

ISSN (print) / ISBN 1758-9193

e-ISSN 1758-9193

Journal Alzheimer's Research & Therapy

Quellenangaben Volume: 14, Issue: 1, Article Number: 128

Publisher BioMed Central

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)

Grants Bundesministerium für Bildung und Forschung
Ministerium fur Wissenschaft, Forschung und Kunst Baden-Wurttemberg
Ministerium für Soziales, Gesundheit, Frauen und Familie, Saarland
Bundesministerium für Familie, Senioren, Frauen und Jugend