UC Davis

The purpose of this dissertation is to highlight the role of high-density lipoprotein (HDL) function, structure, and composition across different life stages and how HDL influences health and disease outcomes, from early childhood, to pregnancy, to old age and Alzheimer’s disease (AD) dementia. The dissertation is divided into four chapters with the corresponding objectives:1. The first chapter is a literature review on the role of HDL across the lifespan, particularly in children, during pregnancy, and in the elderly. These populations are often less studied in the context of HDL and health outcomes. 2. In the second chapter we determine whether small-quantity lipid-based nutrient supplements (SQ-LNS) provided to mothers during the second trimester (≤ 20 weeks), postpartum (0 – 6 months), and their children (6-18 months) improved HDL cholesterol efflux capacity (CEC) compared to children of mothers supplemented with the standard iron and folic acid (IFA) supplement. We further explored whether SQ-LNS altered HDL lipidomic and glycoproteomic composition. We found that children in the SQ-LNS group had improved HDL CEC and altered HDL protein glycosylation. CEC was also found to be associated with site-specific glycans on HDL. 3. The third chapter evaluates whether SQ-LNS altered HDL CEC and plasma enzyme activities involved in HDL metabolism of pregnant mothers at 36 weeks gestation and whether these functional metrics are associated with pregnancy outcomes. SQ-LNS did not alter HDL CEC or plasma enzyme activities in mothers, but these metrics were heavily influenced by factors mediated by season at the time of blood draw. 4. In the fourth chapter we determine whether the function and structure of HDL are altered in AD patients compared to non-demented controls and whether these alterations are influenced by apolipoprotein E (APOE) genotype. We found for the first time that changes in HDL function and size were APOE genotype-specific, and that there is a link between HDL function, size, and cognitive function.