Figure 4: Mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease (AD). Hallmarks of AD include the formation of senile plaques composed of β-amyloid (Aβ) and neurofibrillary tangles caused by tau hyperphosphorylation. Amyloid precursor protein (APP) has been reported to translocate and accumulate in mitochondrial membranes and could be cleaved by γ-secretase to form Aβ, leading to mitochondrial dysfunction. The accumulation of redox active iron in senile plaques and neurofibrillary tangles, as well as the overall increased iron levels in mitochondria, leads to ROS generation and oxidative stress. The mitochondrial membrane potential () is also disrupted in AD. Mitochondrial DNA (mtDNA) suffers oxidative damage in which there are increased mutations to mtDNA with reduced transcription and mtDNA number. Mitochondria in AD also have disrupted mitochondrial fusion whereby the interaction between Aβ and DRP1 promotes mitochondrial fission and subsequent mitochondrial fragmentation. In neurons, there is the loss and dysregulation of synaptic mitochondria, which leads to the impairment of mitochondrial anterograde transport. Finally, mitochondrial dysfunction in AD can lead to apoptosis through cytochrome c release.