title: 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.affiliation: Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. anunomura@yamanashi.ac.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Toshio
authors.initials: T
authors.lastname: Tamaoki
authors.forename: Koich
authors.initials: K
authors.lastname: Tanaka
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Motohashi
authors.forename: Masao
authors.initials: M
authors.lastname: Nakamura
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Hyoung-gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000502:physiology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009696:Nucleic Acids / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D009696:Nucleic Acids; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D006151:Guanosine; C046215:8-hydroxyguanosine