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. 2008 Aug 15;283(33):22550-6.
doi: 10.1074/jbc.M802088200. Epub 2008 May 27.

Antibodies to potato virus Y bind the amyloid beta peptide: immunohistochemical and NMR studies

Robert P Friedland  1 , Johnathan M Tedesco, Andrea C Wilson, Craig S Atwood, Mark A Smith, George Perry, Michael G Zagorski
Affiliations

Antibodies to potato virus Y bind the amyloid beta peptide: immunohistochemical and NMR studies

Robert P Friedland et al. J Biol Chem. .

Abstract

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

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Figures

FIGURE 1.
FIGURE 1.
Primary amino acid sequences of the Aβ-(1–40) and Aβ-(1–42) peptides. The residues shown in red show homology to the PVY protein. The sequence of the N-terminal region of the PVY strain is H2N-DDEFELDSXYEVH-HQXXXXXANDTIDAGGSNK (where X is an unspecified amino acid on PVY) (BLAST, NCBI, and National Institutes of Health).
FIGURE 2.
FIGURE 2.
Enzyme-linked immunosorbent assay data for plated synthetic peptide (PVY-(52–77)) probed with each of the specified antisera (A) and plated Aβ probed with each of the different antisera (B). PBS, phosphate-buffered saline. Leaf material refers to leaf infected with PVY.
FIGURE 3.
FIGURE 3.
Antibodies raised against PVY-(52–77) (A) or the infected control (C) bind to neurofibrillary tangles, senile plaques, and neurons in AD (B) and to neurons in control cases (D).
FIGURE 4.
FIGURE 4.
Expanded 1H-15N heteronuclear single quantum coherence spectral regions showing the backbone NH signals of the Aβ-(1–40) and Aβ-(1–42) peptides (50 mm) in aqueous phosphate buffer (5 mm, pH 7. 3, 5 °C). Red peaks correspond to the peptides alone, whereas blue peaks are the peptides plus 1:50 molar eq of anti-PVY IgG polyclonal antibody. The peaks undergoing significant chemical shift movements are labeled.
FIGURE 5.
FIGURE 5.
Graphical representation of the 1H chemical shift movements of the Aβ-(1–40) and Aβ-(1–42) peptides with PVY.
FIGURE 6.
FIGURE 6.
Graphical representation of the 15N chemical shift movements of the Aβ-(1–40) and Aβ-(1–42) peptides with PVY.
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