The association of high-density lipoprotein cargo proteins with brain volume in older adults in the Atherosclerosis Risk in Communities (ARIC)

Background High-density lipoprotein (HDL) modulates the blood-brain barrier and cerebrovascular integrity, likely influencing the risk of Alzheimer's disease (AD), neurodegeneration, and cognitive decline. Objective This study aims to identify HDL protein cargo associated with brain amyloid deposition and brain volume in regions vulnerable to AD pathology in older adults. Methods HDL was separated from the plasma of 65 non-demented participants of the Atherosclerosis Risk in Communities (ARIC) study using a fast protein liquid chromatography method. HDL cargo proteins were measured using a label-free, untargeted proteomic method based on mass spectrometry and data-independent acquisition. Linear regression with multiple imputations assessed the associations between each HDL cargo protein (log2-transformed) and brain amyloid deposition or temporal-parietal meta-ROI volume, adjusting for covariates. Results The mean (SD) age of the participants was 76.3 (5.4) years old, 53.8% (35/65) female, 30.8% (20/65) black, and 28.1% (18/64, 1 missing) APOE4 carriers. We found few HDL cargo proteins associated with brain amyloid deposition and considerably more HDL cargo proteins associated with temporal-parietal meta-ROI volume. Two HDL cargo proteins mostly associated with temporoparietal meta-ROI volume were fibrinogen B (FGB) and plasminogen (PLG). A doubling of FGB in HDL was associated with a greater temporoparietal meta-ROI volume of 1638 mm(3) (95% CI [688, 2589]). In comparison, a doubling of PLG in HDL was associated with a lower temporoparietal meta-ROI of 2025 mm(3) (95% CI [-3669, -1034]). Conclusions This study suggests that HDL cargo proteins associated with temporal-parietal meta-ROI volume are involved in complement and coagulation pathways.