Oxidative Damage Is the Earliest Event in Alzheimer Disease

Akihiko Nunomura; George Perry; Gjumrakch Aliev; Keisuke Hirai; Atsushi Takeda; Elizabeth K. Balraj; Paul K. Jones; Hossein Ghanbari; Takafumi Wataya; Shun Shimohama; Shigeru Chiba; Craig Atwood; Robert B. Petersen; Mark A. Smith

doi:10.1093/jnen/60.8.759

Abstract

Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurodegeneration in AD, we investigated the relationship between neuronal 8OHG and nitrotyrosine and histological and clinical variables, i.e. amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT), as well as duration of dementia and apolipoprotein E (ApoE) genotype. Our findings show that oxidative damage is quantitatively greatest early in the disease and reduces with disease progression. Surprisingly, we found that increases in A beta deposition are associated with decreased oxidative damage. These relationships are more significant in ApoE epsilon4 carriers. Moreover, neurons with NFT show a 40%-56% decrease in relative 8OHG levels compared with neurons free of NFT. Our observations indicate that increased oxidative damage is an early event in AD that decreases with disease progression and lesion formation. These findings suggest that AD is associated with compensatory changes that reduce damage from reactive oxygen.

Keywords

Oxidative stressNeurodegenerationNitrotyrosineApolipoprotein ENeurofibrillary tangleOxidative phosphorylationLesionAlzheimer's diseaseDiseaseDementiaPathologyInternal medicineBiologyMedicineBiochemistrySenile plaques

Affiliated Institutions

Related Publications

Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.

Warren J. Strittmatter , Ann M. Saunders , D. E. Schmechel +4 more

Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrosp...

1993 Proceedings of the National Academy o... 4230 citations

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

D. E. Schmechel , Ann M. Saunders , Warren J. Strittmatter +6 more

Amyloid beta-peptide (A beta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that common...

1993 Proceedings of the National Academy o... 1509 citations

Cerebral amyloid deposition and diffuse plaques in ``normal'' aging

John C. Morris , Martha Storandt , Daniel W. McKeel +4 more

The presence of senile plaques in the neocortex of apparently nondemented elderly persons often is accepted as part of "normal" aging. Alternatively, because cerebral deposition...

1996 Neurology 594 citations

Alzheimer disease

David S. Knopman , Hélène Amieva , Ronald C. Petersen +5 more

Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neu...

2021 Nature Reviews Disease Primers 2050 citations

Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease

Ann M. Saunders , Warren J. Strittmatter , D. E. Schmechel +11 more

Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid ...

1993 Neurology 3775 citations

Publication Info

Year: 2001
Type: article
Volume: 60
Issue: 8
Pages: 759-767
Citations: 1839
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

Oxidative Damage Is the Earliest Event in Alzheimer Disease

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1839

OpenAlex

Cite This

APA Style

                            
                                
                                    Akihiko Nunomura, 
                                
                                    George Perry, 
                                
                                    Gjumrakch Aliev
                                
                                et al.
                            
                            (2001). 
                            Oxidative Damage Is the Earliest Event in Alzheimer Disease. 
                            Journal of Neuropathology & Experimental Neurology
                            , 60
                            (8)
                            , 759-767.
                            https://doi.org/10.1093/jnen/60.8.759
                        

Identifiers

DOI: 10.1093/jnen/60.8.759