Intraneuronal amyloid beta accumulation and oxidative damage to nucleic acids in Alzheimer disease.

Abstract

In an analysis of amyloid pathology in Alzheimer disease, we used an in situ approach to identify amyloid-beta (Abeta) accumulation and oxidative damage to nucleic acids in postmortem brain tissue of the hippocampal formation from subjects with Alzheimer disease. When carboxyl-terminal-specific antibodies directed against Abeta40 and Abeta42 were used for immunocytochemical analyses, Abeta42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to Abeta-oligomer. In comparison to the Abeta42-positive neurons, neurons bearing oxidative damage to nucleic acids were more widely distributed in the hippocampus. Comparative density measurements of the immunoreactivity revealed that levels of intraneuronal Abeta42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside (r=- 0.61, p<0.02). Together with recent evidence that the Abeta peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric Abeta may be a compensatory response in neurons to oxidative stress in Alzheimer disease.

• Authors: Akihiko Nunomura, Toshio Tamaoki, Koich Tanaka, Nobutaka Motohashi, Masao Nakamura, Takaaki Hayashi, Haruyasu Yamaguchi, Shun Shimohama, Hyoung-gon Lee, Xiongwei Zhu, Mark A Smith, George Perry
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 37 Issue 3 Pg. 731-7 (Mar 2010) ISSN: 1095-953X [Electronic] United States
• PMID: 20034567 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Nucleic Acids
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• Guanosine
• 8-hydroxyguanosine

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (genetics, metabolism, physiopathology)
• Amyloid beta-Peptides (metabolism)
• Brain (metabolism, pathology, physiopathology)
• Cell Nucleus (genetics, metabolism, pathology)
• Cytoplasm (metabolism, pathology)
• Cytoprotection (physiology)
• Female
• Guanosine (analogs & derivatives, metabolism)
• Humans
• Immunohistochemistry
• Male
• Nerve Degeneration (genetics, metabolism, physiopathology)
• Neurons (metabolism, pathology)
• Nucleic Acids (metabolism)
• Oxidative Stress (physiology)
• Peptide Fragments (metabolism)