Retroelement expression profiles in peripheral CD18/ ITGB2 high monocytes correlate with early Alzheimer’s Disease 2966

Abstract Description Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neuronal dysfunction and cognitive decline. Emerging evidence demonstrates the impact of peripheral and local immunity on neurocognitive function in AD. In the periphery, monocytes capture and reciprocate proinflammatory signals in response to AD-related beta-amyloids (BAs). Increased monocyte trafficking towards the central nervous system by peripheral BA peptides may precede AD-related neuroinflammation in the brain. CD18 Integrin (ITGB2) regulates immune cell signaling and trafficking, and in AD, permits BA recognition by immune cells of monocytic origin. Retroelements, such as human endogenous retroviruses (HERVs), reflect strong AD-specific expression profiles, and we hypothesized that retroelement activity may better define the cellular biology of BA-ITGB2 immune axes in AD. We analyzed retroelement and gene expression patterns from sequenced single cells from the peripheral blood of early AD, late AD, and age matched controls. We found high ITGB2 expression in CD14+ monocytes from early AD patients. We observed that HERV expression strongly correlated with ITGB2 expression in various immune cell subsets, demonstrating a strong positive correlation in CD14+ monocytes. Our findings link AD-specific HERV-expression profiles to the integrin-mediated responses which mediate BA clearance and immune responses in the periphery of AD patients. Funding Sources This study was funded by NIH Grant #R56AG078970 Topic Categories Neuroimmunology (NEUR)