APP and Alzheimer disease: This finding is consistent with a recent mouse study that has shown that the genetic risk of AD is functionally associated with the microglia response to Aβ pathology, not to tau pathology (Sierksma et al., 2020), suggesting that Aβ pathology is upstream of tau pathology, and the immune response of AD1 microglia to Aβ pathology is involved in the onset and progression of AD.