APP and Alzheimer disease: Consistent with the so-called “cholinergic hypothesis” of AD [50], several APP transgenic mouse models reproduce cholinergic neurodegeneration as evidenced by dystrophic neurites, decreased fiber density in the hippocampus and cortex, and reductions in the medial septum and basal forebrain neuron volume/number [51], [52], [53], [54]; however, the mechanisms for cholinergic neuron loss is yet largely unknown.