Oxidative Damage is Correlated with Mitochondrial Autophagy

Alzheimer disease (AD) and aging are marked by oxidative damage and mitochondrial abnormalities. Since mitochondria can play a critical role in oxidative damage, we conducted this study to identify the relationship of oxidized RNA, 8‐hydroxyguanosine (8OHG), and mitochondrial DNA (mtDNA) accumulation in AD and aging individuals. Abnormalities were examined by using densitometry of hippocampal pyramidal neurons: mtDNA accumulation as a marker of mitophagy and oxidative damage by 8OHG. Among aging individuals, oxidative damage and mtDNA were highly correlated (r2 = 0.86). While both 8OHG and mtDNA were at higher levels in AD individuals, they were uncorrelated (r2 = 0.06). In contrast, as we found before, oxidative damage was inversely correlated with amyloid‐β; it was unrelated in normal aging individuals. These results suggest that oxidative damage is directly related to mitophagy in aging individuals. With the onset of AD, amyloid‐β plays a strong antioxidant role. These findings indicate that the onset of AD is marked by a pleotrophic change in oxidative stress, one characterized by a change from mitochondria to amyloid‐β dependency.