rna oxidation adducts 8-ohg and 8-oha change with aβ42 levels in late-stage alzheimers diseaserna氧化加合物8-ohg aβ42水平8-oha变化和晚期老年痴呆症.pdfVIP

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rna oxidation adducts 8-ohg and 8-oha change with aβ42 levels in late-stage alzheimers diseaserna氧化加合物8-ohg aβ42水平8-oha变化和晚期老年痴呆症.pdf

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rna oxidation adducts 8-ohg and 8-oha change with aβ42 levels in late-stage alzheimers diseaserna氧化加合物8-ohg aβ42水平8-oha变化和晚期老年痴呆症

RNA Oxidation Adducts 8-OHG and 8-OHA Change with Ab42 Levels in Late-Stage Alzheimer’s Disease Adam M. Weidner1,2., Melissa A. Bradley1,2., Tina L. Beckett1., Dana M. Niedowicz1,2, Amy L. S. 1,4 1 1,2 1,3 1,2 Dowling , Sergey V. Matveev , Harry LeVine III , Mark A. Lovell *, M. Paul Murphy * 1 Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America, 2 Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America, 3 Department of Chemistry, University of Kentucky, Lexington, Kentucky, United States of America, 4 Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, United States of America Abstract While research supports amyloid-b (Ab) 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 Ab. 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 sho