Growing evidence suggests that the accumulation of APP and Aβ in synaptic mitochondria from post-mortem AD brains, as well as cellular and transgenic mouse models [146,147,148], due to interactions with proteins essential for proper organelle function [79,83,149,150,151], causes both structural and functional mitochondrial damage, triggers synaptic lesions, interrupting synaptic transmission [152,153], and ultimately prevents neurons from functioning normally [154] (Figure 2). This evidence concerns the gene APP and Alzheimer disease.