Osteopontin-producing microglia contribute to Alzheimer’s disease (AD) pathology and severity

We define a pathogenic subset of microglia that is distinguished by expression of the CD11c protein and by production of osteopontin (OPN). OPN production by this CD11c+ microglial subset correlates positively with disease pathology and severity in the 5XFAD mouse model and in AD patients. Genetic ablation of OPN in 5XFAD mice leads to reduced development of pro-inflammatory CD11c+ microglia, increased amyloid beta (Aβ) phagocytosis and improved cognitive function. Transcriptome profile of CD11c+ microglial subset of 9-mo old 5XFAD mice versus OPN-KO.5XFAD mice and the mRNA profile of CD11c+ microglia versus CD11c- microglia of 9-mo old 5XFAD mice.