TY - JOUR
T1 - RNA oxidation adducts 8-OHG and 8-OHA change with Aβ 42 levels in late-stage Alzheimer's disease
AU - Weidner, Adam M.
AU - Bradley, Melissa A.
AU - Beckett, Tina L.
AU - Niedowicz, Dana M.
AU - Dowling, Amy L.S.
AU - Matveev, Sergey V.
AU - LeVine, Harry
AU - Lovell, Mark A.
AU - Murphy, M. Paul
PY - 2011/9/20
Y1 - 2011/9/20
N2 - 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 Aβ 42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ 42 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.
AB - 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 Aβ 42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ 42 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.
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U2 - 10.1371/journal.pone.0024930
DO - 10.1371/journal.pone.0024930
M3 - Article
C2 - 21949792
AN - SCOPUS:80052934408
VL - 6
IS - 9
M1 - e24930
ER -