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

• Published in: Neurobiology of disease Vol. 37; no. 3; pp. 731 - 737
• Main Authors: Nunomura, Akihiko, Tamaoki, Toshio, Tanaka, Koich, Motohashi, Nobutaka, Nakamura, Masao, Hayashi, Takaaki, Yamaguchi, Haruyasu, Shimohama, Shun, Lee, Hyoung-gon, Zhu, Xiongwei, Smith, Mark A., Perry, George
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2010; Elsevier
• Subjects: 8-Hydroxyguanosine; Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - metabolism; Brain - metabolism; Brain - pathology; Brain - physiopathology; Cell Nucleus - genetics; Cell Nucleus - metabolism; Cell Nucleus - pathology; Cytoplasm - metabolism; Cytoplasm - pathology; Cytoprotection - physiology; Female; Guanosine - analogs & derivatives; Guanosine - metabolism; Humans; Immunohistochemistry; Intraneuronal amyloid-β; Male; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurology; Neurons - metabolism; Neurons - pathology; Nucleic acids; Nucleic Acids - metabolism; Oligomer; Oxidative stress; Oxidative Stress - physiology; Peptide Fragments - metabolism; Oxidative stress; Intraneuronal amyloid-β; Nucleic acids; Oligomer; Alzheimer disease; 8-Hydroxyguanosine
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2009.12.012

In an analysis of amyloid pathology in Alzheimer disease, we used an in situ approach to identify amyloid-β (Aβ) 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 Aβ40 and Aβ42 were used for immunocytochemical analyses, Aβ42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to Aβ-oligomer. In comparison to the Aβ42-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 Aβ42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside ( r = − 0.61, p < 0.02). Together with recent evidence that the Aβ peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric Aβ may be a compensatory response in neurons to oxidative stress in Alzheimer disease.