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

in an analysis of amyloid pathology in Alzheimer disease, we used an in situ approach to identify amyloid-beta (A beta) 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 A beta 40 and A beta 42 were used for immunocytochemical analyses, A beta 42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to A beta-oligomer. In comparison to the A beta 42-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 A beta 42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside (r= -0.61, p<0.02). Together with recent evidence that the A beta peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric A beta may be a compensatory response in neurons to oxidative stress in Alzheimer disease. (C) 2009 Elsevier Inc. All rights reserved.