In line with this notion, APOE has been shown to promote AD progression in mice bearing pathogenic APP and presenilin 1 (PSEN1, best known as PS1) variants (namely, APP-PS1 mice)52 and P301S mice53, a neurodegenerative mechanism mapping to the subset of microglia that exhibit a common disease-associated phenotype in mice and humans52,54. Here, APP is linked to Alzheimer disease.