Pathologic mitophagy in neurites induces mitochondrial plaques in AD mouse brains [XD_MPP_Hippocampus]

Using a newly established AD mitophagy reporter mouse model (APP/PSEN1/mt-keima), we find that the basal mitophagy of neuronal soma in the hippocampal CA1 region of AD mice is selectively impaired. Pathologic mitophagy is highly activated in neurites in both the cortex and hippocampus regions of AD mice, with abnormal accumulation of mitochondria.

These aberrantly accumulated mitochondria are fragmented and trigger massive formation of mitophagosomes and mitolysomes. However, the degradation of mitochondria is incomplete, likely due to inadequate maturation of lysosomal protease and de-acidification of lysosomes, leading to the mitochondrial accumulation within autophagic vacuoles. The resulting swollen neurites coalesce into structures containing mitochondria at different stages of degradation, that we term mitochondrial plaques (MPs).