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Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease

Lookup NU author(s): Professor Raj KalariaORCiD


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An in situ approach was used to identify the oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the frontal cortex of familial Alzheimer's disease (FAD) with a mutation in presenilin-1 (PS-1) or amyloid protein precursor (AOPP) gene (n = 13, age 47-81 years). Neurons with marked 80HG immunoreaction in the cytoplasm were widely distributed in the superior/middle frontal gyros of FAD. Relative intensity measurements of neuronal 80HG immunoreactivity showed that there was a significant increase in FAD compared with controls (n = 15, age 59-81 years), while there was no difference in relative 80HG between the PS-1 and the AOPP FAD. Interestingly, a presymptomatic case carrying a PS-1 mutation showed a considerable level of relative 8OHG, and the increased levels of neuronal 80HG in FAD were more prominent in cases with a lower percentage area of Abeta42 burden. These results suggest that oxidative stress is an early event involved in the pathological cascade of FAD. (C) 2004 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Nunomura A, Chiba S, Lippa CF, Cras P, Kalaria RN, Takeda A, Honda K, Smith MA, Perry G

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2004

Volume: 17

Issue: 1

Pages: 108-113

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Academic Press


DOI: 10.1016/j.nbd.2004.06.003


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