APP and Alzheimer disease: Recently, a similar phenotype of diffuse plaques and impaired microglial clustering around plaques were found in another APP-overexpressing AD mouse model (Meilandt et al., 2020), which has deficiency in triggering receptor expressed on myeloid cells 2 (Trem2), a myeloid-specific AD risk gene that regulates microglial proliferation, phagocytosis, and metabolism (Deczkowska et al., 2020).