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

Abstract

AbstractBackgroundAlzheimer’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.MethodWe 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.ResultBiomarkers 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<0.01). On univariate analyses, one inflammatory PC loading positively on G‐CSF and RANTES associated with lesser concentrations of p‐Tau181, NfL, and GFAP (all p<0.05). An amino acid biomarker PC loading positively on hydrophobic amino acids associated with lesser concentrations of NfL and GFAP (all p<0.001). An inflammatory PC loading positively on TNF‐α, TNFR‐I, TNFR‐II and IL‐6, and d‐dimer associated with greater concentrations of p‐Tau181 and NfL (all p<0.01). An acylcarnitine PC loading positively on short‐chain acylcarnitines was associated with greater concentrations of NfL (p<0.001). None of the biomarker PCs significantly associated with the Aβ‐42/Aβ‐40 ratio.ConclusionIn community‐dwelling older adults, biomarker PCs loading on G‐CSF, RANTES, and hydrophobic amino acids were associated with lesser concentrations of some plasma ADRD biomarkers, while an inflammatory PC loading on TNF‐α, TNFR‐I, TNFR‐II, and VCAM‐1 was associated with greater concentrations. Our findings provide insight into the association of inflammatory and metabolic biomarkers with plasma biomarkers of ADRD pathology.