In 5×FAD mice, which overexpress APP with the Swedish (K670N, M671L), Florida (I716V) and London (V717I) mutations, and PS1 with M146L and L286V mutations, Rag deficiency exacerbates AD due to loss of nonspecific immunoglobulin that activates microglial phagocytosis and consequent clearance of Aβ plaques21. Here, PSEN1 is linked to Alzheimer disease.