Abstract
While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain regions (Brodmann's Area 9, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri), we found that the RNA adduct 8-hydroxyguanine (8-OHG) decreased, while 8-hydroxyadenine (8-OHA) increased in AD. The cerebellum, which is generally spared in AD, did not show disease related changes, and no RNA adducts correlated with the number of plaques or tangles. Multiple regression analysis revealed that SDS-soluble Aβ42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ42 was the best predictor of changes in 8-OHA. This study indicates that although there is a connection between AD related neuropathology and RNA oxidation, this relationship is not straightforward.
Highlights
With an increase in the aging population, neurodegenerative diseases are becoming more prevalent
We analyzed the relationship between these RNA adducts and the common neuropathological markers used to diagnose Alzheimer’s disease (AD)
A correlational analysis of the data did not indicate any significant relationships between any of these markers and any of the five RNA adducts (p.0.1 in all cases). This was true across all cases, even when the analysis was restricted to AD cases alone
Summary
With an increase in the aging population, neurodegenerative diseases are becoming more prevalent. An increase in oxidative stress found in the form of oxidized DNA, RNA, and protein adducts may contribute to the progression of the disease [9,10].
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