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: Akihiko Nunomura, Shigeru Chiba, Carol F Lippa, Patrick Cras, Rajesh N Kalaria, Atsushi Takeda, Kazuhiro Honda, Mark A Smith, George Perry
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 17 Issue 1 Pg. 108-13 (Oct 2004) ISSN: 0969-9961 [Print] United States
• PMID: 15350971 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Guanosine
• 8-hydroxyguanosine
• RNA

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism, pathology)
• Brain (metabolism, pathology)
• Female
• Guanosine (analogs & derivatives, genetics, metabolism)
• Humans
• Male
• Middle Aged
• Neurons (metabolism, pathology)
• Oxidation-Reduction
• RNA (metabolism)