Figure 2. Mitochondrial dysfunction and compromised mitophagy in AD.

In unaffected neurons, healthy mitochondria are distributed through the neuron. When they become dysfunctional (shown here in purple), they are packaged into autophagosomes and trafficked to lysosomes to be degraded. In AD affected neurons, comprised mitophagy causes decreased energy production and increased oxidative stress. This leads to increased amyloidogenic processing of APP by β-secretase and γ-secretase/PS1 and, in parallel, the accumulation of pTau aggregates. Pathogenic Aβ and pTau can impair mitophagy, leading to a subsequent increase in damaged mitochondria, and initiation of a self-propagating vicious cycle. Mechanisms of compromised mitophagy in AD are still elusive.