CD36-mediated innate immune memory of brain vascular endothelial cells and Alzheimer’s disease 9017

Abstract Description Vascular endothelial cells (ECs) are emerging as a unique type of innate immune cells. CD36, an innate immunity receptor, might be critical for regulating innate immunity of the vascular ECs in the brain. To test this, we created EC-specific CD36 knockout translating ribosome affinity purification (TRAP) and control mice. Using ribosome-bound mRNA directly isolated from the brain vascular endothelia in vivo, we performed deep RNA-seq and transcriptional profiling. Our studies demonstrated that gene signatures related to innate immune memory were downregulated in CD36-deficient endothelia, accompanied by changed expression of genes related to immune responses and fatty acid metabolism. Intriguingly, further analysis of single cell RNA-seq data of patients indicated a significant contribution of a unique subset of CD36-positive brain ECs to the progression of Alzheimer’s disease. Our studies indicate that CD36-mediated fatty acid reprogramming might bridge innate immune memory in brain ECs to the pathogenesis of Alzheimer’s disease. Funding Sources American Heart Association Transformational Project Award 24TPA1293301; NIH/NHLBI Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)