APP and early-onset autosomal dominant Alzheimer disease: While transgenic mice overexpressing human amyloid precursor protein (App) with various mutations have yielded a lot of our current understanding of Alzheimer’s disease, these mice often develop artificial phenotypes related to the unphysiological overexpression of APP levels and its proteolytic fragments.29 To overcome this, we used two App knock-in mouse models previously generated as ‘models of preclinical Alzheimer’s disease’:30 the AppNL-F and the AppNL-G-F mice.