UC San Diego

Alzheimer’s disease (AD) is a neurodegenerative disease that involves hallmark pathologies like amyloid beta plaques, tau tangles, and neuroinflammation. One class of neuroinflammatory molecules is oxidized phospholipids (OxPL). OxPL are toxic moieties generated under oxidative stress, and cause immune cell hyperactivity in many disease models. Traditionally, mass spectrometry has been used to measure OxPL, but our lab recently developed an enzyme-linked immunosorbent assay (ELISA) using the antibody E06. However, this assay suffers from a number of methodological problems and lacks a reliable source of reagents. This project aims to develop and validate a revised competitive ELISA to measure OxPL in plasma using E06, a natural antibody that binds specifically to OxPL but not normal phospholipids, and apply the assay to measure plasma OxPL level of an AD mouse model, PSAPP+ mice that generate amyloid beta. Immunostainings were also performed in these mice with E06 to detect and quantify hippocampal OxPL. These studies measured the OxPL level changes to see if there was OxPL accumulation in AD progression. Analysis of plasma of aging control and PSAPP+ mice with the competitive ELISA demonstrated a statistically insignificant but clear trend of increasing plasma OxPL level in PSAPP+ mice compared to healthy controls, especially in later stages. Furthermore, PSAPP+ mice have significantly higher hippocampal OxPL levels that was weakly correlated with their amyloid beta deposits. These results provide preliminary support for the hypothesis that plasma and brain OxPL levels might be biomarkers for the disease and might be involved in the pathogenesis of AD.