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Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Bradley-Whitman MA and Lovell MA

Studies of oxidative damage during the progression of Alzheimer’s Disease (AD) suggest a central role in disease pathogenesis. To determine if RNA oxidation increases in the progression of AD levels of oxidized bases from RNA from the superior and middle temporal gyri (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) throughout the progression of AD including subjects with mild cognitive impairment (MCI), preclinical AD (PCAD), late-stage AD (LAD), diseased control (DC) (Frontotemporal Dementia (FTD) and Dementia with Lewy Bodies (DLB)), and agematched normal control subjects (NC) were analyzed by gas chromatography mass spectrometry. Median levels of multiple RNA adducts were significantly (p<0.05) elevated in the SMTG, IPL, and CER in multiple stages of AD and in DC subjects. Elevated levels of 4,6-diamino-5-foramidopyrimidine (FapyA) suggest a hypoxic environment early in the progression of AD and in DC subjects. Overall, these data suggest oxidative damage is an early event not only in the pathogenesis of AD, but is present in neurodegenerative diseases in general.