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Gerontology and Ageing ; Social Sciences ; Alzheimer's Disease


Brain MRI volumes measuring brain atrophy have been associated with risks for Alzheimer’s Disease (AD) and related dementia. Inflammatory biomarkers associated with brain MRI volumes may provide insight into the neuroinflammation associated with these diseases. The study aim is to identify circulating inflammatory biomarkers associated with total and regional brain MRI volumes in the Framingham Heart Study Offspring cohort. Participants (N=662, 52% female, mean age 62 years) free of dementia and stroke at the time of blood draw and who had MRI measures within five years were profiled using the OLINK Proteomics inflammation panel. Pairwise cross-sectional associations between 68 biomarkers and eight brain MRI volumes were investigated using linear mixed-effect models accommodating familial correlations and adjusting for covariates (age, age2, sex, time between blood draw and MRI measurement, age-sex interaction, and number of APOE ε2 and ε4 alleles), using FDR≤0.1 to declare significance. APOE genotype-stratified analyses were performed to explore effect modification. Higher levels of 8 proteins were significantly associated with smaller total brain volumes (TCBV), including CDCP1, HGF, IL6, IL8, MMP10, OPG, VEGFA, and 4E-BP1. Higher levels of SCF and TWEAK were significantly associated with larger TCBV, and higher levels of SCF were also associated with larger parietal gray matter volume. In APOE ε4 carriers, higher levels of IFNγ were associated with greater white matter hyperintensity volumes. Consistent with our findings, SCF has been shown to have neuroprotective effects in animal models. Further studies are needed to confirm these potential risk and protective factors and to elucidate mechanisms.


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© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.