RES ULTS AND DIS CUS SION Aβ-reactive myeloid cells derive from brain-resident microglia

It has been proposed that the TREM2-dependent microglial response to Aβ plaques in APP PS1-21 mice relies on the recruitment of blood monocytes (Jay et al., 2015). We first determined whether blood monocytes in 5XFAD mice express TREM2 and hence might respond to putative TREM2 ligands present in peripheral blood during Aβ accumulation. Staining of monocytes from 5XFAD and wild-type mice with anti-TREM2 revealed no detectable expression of TREM2 (Fig. 1 A). However, it remained possible that monocytes up-regulate TREM2 upon infiltrating the brain and, therefore, TREM2 would be required for clustering of infiltrating monocyte around Aβ plaques. To definitively test for contribution of blood