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Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort |
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| Authors: | Jiachen Chen Margaret F Doyle Yuan Fang Jesse Mez Paul K Crane Phoebe Scollard ADSP Data Harmonization Consortium Cognitive Harmonization Core Claudia L Satizabal Michael L Alosco Wei Qiao Qiu Joanne M Murabito Kathryn L Lunetta |
| Institution: | 1. Boston University School of Public Health, Department of Biostatistics, Boston, Massachusetts, USA;2. Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA;3. Boston University Chobanian & Avedisian School of Medicine, Boston University Alzheimer's Disease Research Center and CTE Center, Boston, Massachusetts, USA
Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA Framingham Heart Study, National Heart, Lung, and Blood Institute and Boston University Chobanian & Avedisian School of Medicine, Framingham, Massachusetts, USA;4. Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA;5. Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA University of Texas Health Science Center at San Antonio, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, Texas, USA;6. Boston University Chobanian & Avedisian School of Medicine, Boston University Alzheimer's Disease Research Center and CTE Center, Boston, Massachusetts, USA Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA;7. Boston University Chobanian & Avedisian School of Medicine, Boston University Alzheimer's Disease Research Center and CTE Center, Boston, Massachusetts, USA Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA Boston University Chobanian & Avedisian School of Medicine, Department of Pharmacology & Experimental Therapeutics, Boston, Massachusetts, USA;8. Framingham Heart Study, National Heart, Lung, and Blood Institute and Boston University Chobanian & Avedisian School of Medicine, Framingham, Massachusetts, USA Department of Medicine, Section of General Internal Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts, USA |
| Abstract: | Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well-characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia-free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross-sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all-cause and AD dementia during up to 20 years of follow-up were tested. APOE genotype-stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all-cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline. |
| Keywords: | Alzheimer's disease cognitive aging peripheral inflammation protein biomarkers |