APP and early-onset autosomal dominant Alzheimer disease: It has also been shown that, in fibroblasts from Down syndrome patients, which are predisposed to early-onset Alzheimer’s disease, the extra chromosome 21 encoding the amyloid precursor protein (APP) causes increased levels of the β-cleaved carboxy-terminal fragment of APP which impairs lysosomal acidification and function through the inhibition of the v-ATPase as well as dysfunctional mitophagy [26].