Studies have indicated that prolonged exposure to toxic Aβ peptides downregulates expression of phagocytic receptors such as CD47, CD36 and RAGE [45], impairs microglial autophagy and induces lysosomal dysfunction in AD [46], an observation corroborated in-vivo by significant alteration of endocytosis/phagocytosis and AGE-RAGE signaling pathways (Supplemental Fig. 3) coupled with reduced fAβ uptake and lysosomal acidification in CD11b+ microglia from 5xFAD;Cx3cr1−/− mice in this study (Supplemental Fig. 6, Fig. 4). This evidence concerns the gene ITGAM and Alzheimer disease.