RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease.
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 obser...
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2011
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oai:doaj.org-article:ea059413b8664dab9a31f4f23215b99d2021-11-04T06:08:12ZRNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease.1932-620310.1371/journal.pone.0024930https://doaj.org/article/ea059413b8664dab9a31f4f23215b99d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21949792/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203While 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.Adam M WeidnerMelissa A BradleyTina L BeckettDana M NiedowiczAmy L S DowlingSergey V MatveevHarry LeVineMark A LovellM Paul MurphyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24930 (2011) |
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Medicine R Science Q Adam M Weidner Melissa A Bradley Tina L Beckett Dana M Niedowicz Amy L S Dowling Sergey V Matveev Harry LeVine Mark A Lovell M Paul Murphy RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease. |
| description |
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. |
| format |
article |
| author |
Adam M Weidner Melissa A Bradley Tina L Beckett Dana M Niedowicz Amy L S Dowling Sergey V Matveev Harry LeVine Mark A Lovell M Paul Murphy |
| author_facet |
Adam M Weidner Melissa A Bradley Tina L Beckett Dana M Niedowicz Amy L S Dowling Sergey V Matveev Harry LeVine Mark A Lovell M Paul Murphy |
| author_sort |
Adam M Weidner |
| title |
RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease. |
| title_short |
RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease. |
| title_full |
RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease. |
| title_fullStr |
RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease. |
| title_full_unstemmed |
RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer's disease. |
| title_sort |
rna oxidation adducts 8-ohg and 8-oha change with aβ42 levels in late-stage alzheimer's disease. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/ea059413b8664dab9a31f4f23215b99d |
| work_keys_str_mv |
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