APP and Alzheimer disease: Mitochondrial dysfunction, as reported, can precede the accumulation of Aβ deposits.197,198 Normally functioning mitochondria can reduce aberrant amyloid precursor protein (APP) processing and the buildup of Aβ plaques.199 Ye et al. first revealed Parkin-mediated enhancement of mitophagy in mutant hAPP neurons and AD patient’s brains.200 Additionally, cytosolic Parkin in the AD patient’s brains is depleted as the disease progresses, leading to abnormal accumulation of PINK1.