title: Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease.
abstract: 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 beta protein precursor (AbetaPP) gene (n = 13, age 47-81 years). Neurons with marked 8OHG immunoreaction in the cytoplasm were widely distributed in the superior/middle frontal gyrus of FAD. Relative intensity measurements of neuronal 8OHG 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 8OHG between the PS-1 and the AbetaPP FAD. Interestingly, a presymptomatic case carrying a PS-1 mutation showed a considerable level of relative 8OHG, and the increased levels of neuronal 8OHG 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.
authors.affiliation: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan. nuno@asahikawa-med.ac.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Carol F
authors.initials: CF
authors.lastname: Lippa
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Honda
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D012313:RNA / Q000378:metabolism*
chemical_list: D006151:Guanosine; C046215:8-hydroxyguanosine; D012313:RNA