Treatment with C5aR1 antagonist attenuates short‐term hippocampal memory decline and prevents DAM signature in Arctic mice.

Upregulation of complement genes in Alzheimer’s disease (AD) mouse models is associated with inflammation and cognitive decline. Genetic ablation of C5aR1 reduces loss of neuronal complexity and cognition in the Arctic mouse model. Inhibition of C5aR1 with PMX205 has shown success in preclinical studies of AD, reducing recruitment of reactive glia and amyloid deposition in the Tg2576 AD model. However, the molecular and cellular mechanisms underlying this neuroprotection are unclear. Thus, we used single cell RNA‐seq to interrogate gene pathways involved in C5aR1‐mediated deficits in the Arctic mouse model.