Alzheimer's disease (AD) is an age-dependent, incurable mental illness that is associated with the accumulation of aggregates of amyloid-beta (Aβ) and hyperphosphorylated tau fragments (p-tau). Detailed studies on postmortem AD brains, cell lines, and mouse models of AD have shown that numerous cellular alterations, including mitochondrial deficits, synaptic disruption and glial/astrocytic activation, are involved in the disease process. Mitophagy is a cellular process by which damaged/weakened mitochondria are selectively eliminated from the cell. In AD, impairments in mitophagy trigger the gradual accumulation of defective mitochondria. This review will focus on the recent progress in understanding the molecular mechanisms and pathological role of mitophagy and its implications for AD pathogenesis. We will also discuss the novel concept of the regulation of mitophagy as a therapeutic avenue for the prevention and treatment of AD.
Mitochondrion, Volume 59, July 2021,