Fig. 3.

Interactions between mitophagy and APP/Aβ and Tau toxicity. The presence of AD-favoring APP mutations increases Aβ levels. This impairs mitochondrial functions by decreasing the expression of autophagy- and mitophagy-related proteins and genes, decreasing cytochrome c oxidase and ATP levels, decreasing mitochondrial fusion, and increasing fission. All these factors damage mitochondria, as well as promoting Aβ-oriented APP cleavage and accumulation. At the early stages of AD, mitophagy can alleviate this damage. However, as AD progresses, Aβ and abnormal Tau accumulate, eventually compromising mitophagy. As a result, the damaged mitochondria cannot be cleared and therefore accumulate