CD36 scavenger receptor promotes adaptive T-cell CNS infiltration and neuroinflammation in AppSAA knock-in mouse model of Alzheimer’s disease 3485

Abstract Description Microglial activation has been shown to promote the CNS infiltration of immune cells, including CD4+ and CD8+ T cells, that exacerbates neuroinflammation and leads to the loss of synaptic-associated proteins and, ultimately, neuronal damage. Previous studies have shown hydrophobic amyloid beta (Aβ) fibrils bind to CD36 scavenger receptors that induce microglial activation, leading to the CNS inflammatory responses in Alzheimer’s disease (AD). Here, we elucidated the role of CD36 receptor in neuroinflammation in AD by using a novel App knock-in (AppSAA) AD mouse model. AppSAA mice with CD36 receptor deficiency (Cd36KOAppSAA) were generated for this purpose. We observed decreased Aβ plaques and enhanced microglial phagocytic marker, Clec7a, in Cd36KOAppSAA mice compared to AppSAA mice. In addition, single-cell RNA Sequencing (scRNA-seq) results revealed increased numbers of disease-associated microglia, which play an essential role in phagocytosing Aβ plaques, in Cd36KOAppSAA compared to AppSAA mice. Furthermore, we observed reduced microglial activation, decreased inflammatory cytokine expression, and attenuated infiltrating CD8+ T cells in the brain of Cd36KOAppSAA compared to that of AppSAA mice. Altogether, our findings suggest that CD36 receptor activation may promote microglial activation and neuroinflammation that subsequently recruit peripheral CD8+ T cells infiltrating the CNS, resulting in exacerbated Aβ pathology in AD. Topic Categories Neuroimmunology (NEUR)