P3‐029: 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 (80HG), 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 80HG. Among aging individuals, oxidative damage and mtDNA were highly correlated (r2 = 0.86). While both 80HG 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; it was unrelated in normal aging individuals. With the onset of AD, amyloid 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 dependency.