Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease.
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.
Nunomura
Akihiko
A
Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan. nuno@asahikawa-med.ac.jp
Chiba
Shigeru
S
Lippa
Carol F
CF
Cras
Patrick
P
Kalaria
Rajesh N
RN
Takeda
Atsushi
A
Honda
Kazuhiro
K
Smith
Mark A
MA
Perry
George
G
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*
D006151:Guanosine; C046215:8-hydroxyguanosine; D012313:RNA