Fig. 4.

Genetic and pharmacologic therapies or lifestyle interventions targeting mitophagy are potential strategies to prevent and treat AD. Abnormal Tau, APP mutant or Aβ leads to mitochondrial impairments, which in turn aggravate Tau and Aβ pathologies. These pathological changes further compromise mitophagy, which decreases the clearance of damaged mitochondria, forming a vicious cycle. This process triggers the accumulation of damaged mitochondria, consequently decreasing the energy supply to neurons which, along with other processes, leads to neurodegeneration and brain atrophy. However, genetic and pharmacologic therapies or lifestyle interventions, such as exercise and fasting, could induce mitophagy and clear the damaged mitochondria. Thus, these strategies have great potential in preventing and treating AD