Our results indicate that plaque-associated lysosomal activity (CD68 and Amylo-Glo colocalization) seems to decrease with age, especially in the hippocampus, meaning that as AD pathology is exacerbated, microglia become less phagocytic, demonstrating their impaired response to neurodegeneration, which is most probably elicited by the presence of the APOE4 allele. Here, APOE is linked to Alzheimer disease.