While older mice that are deficient in eNOS have been studied as a model of stroke (Cui et al., 2009; Tan et al., 2015) and Alzheimer's disease‐related pathologies (Austin et al., 2013), the results of the present study show evidence of sex‐specific brain pathology in young adulthood, before the onset of overt behavioral abnormalities. This evidence concerns the gene NOS3 and early-onset autosomal dominant Alzheimer disease.