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

Neurobiology of Disease (Oct 2004)

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

Affiliations

Akihiko Nunomura: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Shigeru Chiba: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Carol F. Lippa: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Patrick Cras: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Rajesh N. Kalaria: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Atsushi Takeda: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Kazuhiro Honda: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Mark A. Smith: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
George Perry: Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078-8510, Japan; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium; Wolfson Unit, Institute for Ageing and Health, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK; Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA

Journal volume & issue: Vol. 17, no. 1
pp. 108 – 113

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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