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)
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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Article: Journal article
Document type
Scientific Article
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Keywords
Alzheimer’s Disease ; Biomarker ; Cohort Study ; Dementia ; Inflammation ; Vascular Dementia
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Language
english
Publication Year
2022
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2022
ISSN (print) / ISBN
1758-9193
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1758-9193
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Volume: 14,
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Article Number: 128
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BioMed Central
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London
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-505700-001
A-630700-001
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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
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Erfassungsdatum
2022-11-18