We placed this mutation on the Nos2 knock-out background because inducible nitric oxide synthase has a key role in innate immunity (Bogdan, 2015), and the innate immune response is critical for both the initiation and progression of AD ((Zhang et al., 2013; Kan et al., 2015; Shi and Holtzman, 2018)), However, the expression and activity of human NOS2 are significantly lower than for the mouse Nos2 ((Colton et al., 1996; Mestas and Hughes, 2004)); in order to mimic the human condition we knocked-out Nos2 expression. This evidence concerns the gene NOS2 and Alzheimer disease.