Antibodies to Potato Virus Y Bind the Amyloid β Peptide

Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 08/2008; 283(33):22550-22556. DOI: 10.1074/jbc.M802088200
Source: PubMed Central


Studies in transgenic mice bearing mutated human Alzheimer disease (AD) genes show that active vaccination with the amyloid
β (Aβ) protein or passive immunization with anti-Aβ antibodies has beneficial effects on the development of disease. Although
a trial of Aβ vaccination in humans was halted because of autoimmune meningoencephalitis, favorable effects on Aβ deposition
in the brain and on behavior were seen. Conflicting results have been observed concerning the relationship of circulating
anti-Aβ antibodies and AD. Although these autoantibodies are thought to arise from exposure to Aβ, it is also possible that
homologous proteins may induce antibody synthesis. We propose that the long-standing presence of anti-Aβ antibodies or antibodies
to immunogens homologous to the Aβ 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 Aβ. 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 Aβ 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 Aβ within the Phe4–Ser8 and His13–Leu17 regions. Immune responses generated from dietary exposure to proteins homologous to Aβ may induce antibodies that could influence
the normal physiological processing of the protein and the development or progression of AD.

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Available from: Craig S Atwood

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