Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide. Accumulating evidence indicates that microglia, immune cells in the brain, are involved in the AD pathology, and these cells have received much attention as a key to understanding the mechanism of AD and also to developing its therapeutic strategy. It has recently been shown that microglia are highly heterogenous and that the number of a subpopulation of microglia expressing CD11c (CD11c+ microglia) is increased in the brains of AD patients and mouse models. However, the time course of their appearance in AD models has not been investigated well.
In this study, we immunohistochemically analyzed CD11c expression in microglia using a mouse model harboring three familial AD mutations (APPNL-G-F) that had been crossed with a CD11c reporter mouse line (CD11c-Venus). We found that CD11c+ microglia increased from 3 months of age. At this timepoint, CD11c expression in the hippocampus was observed approximately 10% of total IBA1+ microglia in AD models, which was higher than that in control mice (around 2.5%). Additionally, CD11c+ microglia further increased at 6 months of age (the onset stage). Our results indicate that CD11c+ microglia already respond at the early stage of AD models and suggest that these cells may have a role in the pathogenesis of AD.