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

Akihiko Nunomura, Shigeru Chiba, Carol F. Lippa, Patrick Cras, Rajesh N. Kalaria, Atsushi Takeda, Kazuhiro Honda, Mark A. Smith, George Perry

Research output: Contribution to journalArticlepeer-review

129 Citations (Scopus)

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 β protein precursor (AβPP) 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 AβPP 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 Aβ42 burden. These results suggest that oxidative stress is an early event involved in the pathological cascade of FAD.

Original languageEnglish
Pages (from-to)108-113
Number of pages6
JournalNeurobiology of Disease
Volume17
Issue number1
DOIs
Publication statusPublished - 2004 Oct
Externally publishedYes

Keywords

  • 8-Hydroxyguanosine
  • Amyloid β protein precursor
  • Familial Alzheimer's disease
  • Oxidative stress
  • Presenilin
  • RNA

ASJC Scopus subject areas

  • Neurology

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