Antibodies to potato virus Y bind the amyloid β peptide -: Immunohistochemical and NMR studies

Studies in transgenic mice bearing mutated human Alzheimer disease (AD) genes show that active vaccination with the amyloid beta(A beta) protein or passive immunization with anti-A beta antibodies has beneficial effects on the development of disease. Although a trial of A beta vaccination in humans was halted because of autoimmune meningoencephalitis, favorable effects on A beta deposition in the brain and on behavior were seen. Conflicting results have been observed concerning the relationship of circulating anti-A beta antibodies and AD. Although these autoantibodies are thought to arise from exposure to A beta, it is also possible that homologous proteins may induce antibody synthesis. We propose that the long-standing presence of anti-A beta antibodies or antibodies to immunogens homologous to the A beta protein may produce protective effects. The amino acid sequence of the potato virus Y (PVY) nuclear inclusion b protein is highly homologous to the immunogenic N-terminal region of A beta. PVY infects potatoes and related crops worldwide. Here, we show through immunocytochemistry, enzyme-linked immunosorbent assay, and NMR studies that mice inoculated with PVY develop antibodies that bind to A beta in both neuritic plaques and neurofibrillary tangles, whereas antibodies to material from uninfected potato leaf show only modest levels of background immunoreactivity. NMR data show that the anti-PVY antibody binds to A beta within the Phe(4) - Ser(8) and His(13)-Leu(17) regions. Immune responses generated from dietary exposure to proteins homologous to A beta may induce antibodies that could influence the normal physiological processing of the protein and the development or progression of AD.