Association of plasma inflammatory and metabolic biomarkers with plasma ADRD biomarkers in community‐dwelling older adults

Background Alzheimer’s disease and related dementias (ADRD) are associated with changes in inflammatory and metabolic biomarkers. Here, we evaluated associations among inflammatory and metabolic biomarkers previously‐associated with age related‐morbidity and plasma p‐Tau181, Aβ‐42/Aβ‐40 ratio, neurofilament light (NfL), and glial fibrillary acid protein (GFAP) in community‐dwelling older adults. Method We evaluated cross‐sectional associations of a panel of inflammatory and metabolic biomarkers with plasma ADRD biomarkers – quantified using the Quanterix SIMOA platform – in a subset of older adults from the Duke Performance Across the Lifespan (PALS) study (N=317; Age=75±8.6; MoCA=25±3.4). Inflammatory and metabolic biomarkers included TNF‐α, TNFR‐I, TNFR‐II, d‐dimer, IL‐6, VCAM‐1, G‐CSF, RANTES, MMP3, paraoxonase activity, adiponectin, uric acid, 11 free amino acids, and 45 acylcarnitines. We applied principal components analysis (PCA) separately to the inflammatory biomarkers, amino acids, and acylcarnitines. We used multivariate multiple regression to associate biomarker PCs with ADRD biomarkers, adjusting for age and sex. Result Biomarkers were not normally‐distributed and were log‐transformed prior to PCA. We identified 3 inflammatory principal components (PCs), 5 acylcarnitine PCs, and 2 amino acid PCs. Of these, two inflammatory PCs, one acylcarnitine PC, and one amino acid PC were associated with plasma ADRD biomarkers (all Wilk’s Λ p