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

doi:10.1016/j.nbd.2004.06.003

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 journal › Article › peer-review

131 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 language	English
Pages (from-to)	108-113
Number of pages	6
Journal	Neurobiology of Disease
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.nbd.2004.06.003
Publication status	Published - 2004 Oct
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2004.06.003

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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 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.",

keywords = "8-Hydroxyguanosine, Amyloid β protein precursor, Familial Alzheimer's disease, Oxidative stress, Presenilin, RNA",

author = "Akihiko Nunomura and Shigeru Chiba and Lippa, {Carol F.} and Patrick Cras and Kalaria, {Rajesh N.} and Atsushi Takeda and Kazuhiro Honda and Smith, {Mark A.} and George Perry",

note = "Funding Information: Work in the authors' laboratories is supported by funding from the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (c) 14570902), Alzheimer Association, and National Institute of Health.",

year = "2004",

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AU - Nunomura, Akihiko

AU - Chiba, Shigeru

AU - Lippa, Carol F.

AU - Cras, Patrick

AU - Kalaria, Rajesh N.

AU - Takeda, Atsushi

AU - Honda, Kazuhiro

AU - Smith, Mark A.

AU - Perry, George

N1 - Funding Information: Work in the authors' laboratories is supported by funding from the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (c) 14570902), Alzheimer Association, and National Institute of Health.

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N2 - 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.

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

Abstract

Keywords

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