Correlated Oxidative Stress and Mitochondrial Abnormalities in Aging are Discontinuous with Alzheimer’s Disease

Abstract

Oxidative stress and mitochondrial damage precede Alzheimer’s disease (AD) hallmark pathologies, neurofibrillarytangles (NFT), and senile plaques.Mitochondria’s exact role in oxidation of pyruvate and NADH play a critical role in oxidative damage. We conducted this study to identify the relationship of oxidized RNA, 8--OHG biomarker, and 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 8-OHG. Among aging individuals, 8-OHG and mtDNA accumulation were highly correlated (R2=0.87,p=0.0007). While both 8-OHG and mtDNA were at higher levels in AD individuals, they were uncorrelated (R2=0.4418,p=0.07).In AD individuals, 8-OHG was inversely correlated with amyloid-β, while in aging, there was no significant correlation. These results suggest the discontinuity of similarities between aging and AD. These findings also indicate that the onset of AD is marked by a pleotrophic change in oxidative stress, one characterized by a change from mitochondria degeneration to amyloid-β independency.

Oxidative stress and mitochondrial damage precede Alzheimer�s disease (AD) hallmark pathologies, neurofibrillary tangles (NFT), and senile plaques. Mitochondria�s exact role in oxidation of pyruvate and NADH play a critical role in oxidative damage. We conducted this study to identify the relationship of oxidized RNA, 8-OHG biomarker, and 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 8-OHG. Among aging individuals, 8-OHG and mtDNA accumulation were highly correlated (R2 = 0.87, p=0.0007). While both 8-OHG and mtDNA were at higher levels in AD individuals, they were uncorrelated (R2 = 0.4418, p=0.07). In AD individuals, 8-OHG was inversely correlated with amyloid-?, while in aging, there was no significant correlation. These results suggest the discontinuity of similarities between aging and AD. These findings also indicate that the onset of AD is marked by a pleotrophic change in oxidative stress, one characterized by a change from mitochondria degeneration to amyloid-? independency.