Markesbery and Lovell describe the wide spectrum of oxidative lesions found in both nuclear and mitochondrial DNA, detectable early in the progression of Alzheimer’s disease (AD):
Oxidative damage to DNA may play an important role in aging and neurodegenerative diseases such as Alzheimer’s disease (AD). … In late-stage AD brain, several studies have shown an elevation of the base adducts 8 hydroxyguanine (8-OHG), 8-hydroxyadenine (8-OHA), 5-hydroxycytosine (5-OHC), and 5-hydroxyuracil, a chemical degradation product of cytosine. Several studies have shown a decline in repair of 8-OHG in AD. Most recently, our studies have shown elevated 8-OHG, 8-OHA, and 5,6-diamino-5-formamidopyrimidine in nuclear and mitochondrial DNA in mild cognitive impairment, the earliest detectable form of AD, suggesting that oxidative damage to DNA is an early event in AD and not a secondary phenomenon.
But never fear: PH Reddy reviews the potential value of mitochondrially targeted antioxidant compounds as efficacious, low-side effect therapeutics in AD:
… Recent advances in molecular, cellular, and animal model studies of AD have revealed that amyloid precursor protein derivatives, including amyloid beta (A beta) monomers and oligomers, are likely key factors in tau hyperphosphorylation, mitochondrial oxidative damage, inflammatory changes, and synaptic failure in the brain tissue of AD patients. … Recently, however, there has been a breakthrough. Researchers have recently been able to promote the entry of certain antioxidants-including MitoQ, MitoVitE, MitoPBN, MitoPeroxidase, and amino acid and peptide-based SS tetrapeptides-into mitochondria, several hundred-fold more than do natural antioxidants. Once in the mitochondria, they rapidly neutralize free radicals and decrease mitochondrial toxicity. Thus, mitochondrially targeted antioxidants are promising candidates for treating AD patients.
I love it when a plan comes together.