Autoantibodies to amyloid β-peptide (Aβ) are increased in Alzheimer's disease patients and Aβ antibodies can enhance Aβ neurotoxicity: Implications for disease pathogenesis and vaccine development

Avindra Nath, Elizabeth Hall, Marnia Tuzova, Michael Dobbs, Melina Jones, Caroline Anderson, Jerold Woodward, Zhihong Guo, Weiming Fu, Richard Kryscio, David Wekstein, Charles Smith, William R. Markesbery, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid β peptide (Aβ) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Aβ vaccine in patients with Alzheimer's disease (AD) was halted as the result of serious neurological complications in some patients. We now provide evidence that AD patients exhibit an enhanced immune response to Aβ and that, contrary to expectations, Aβ antibodies enhance the neurotoxic activity of the peptide. Serum titers to Aβ were significantly elevated in AD patients and Aβ antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Aβ in the patients. Aβ antibodies were detected in the serum of old APP mutant transgenic mice with plaque-like Aβ deposits, but not in the serum of younger transgenic or nontransgenic mice. Serum from APP mutant mice potentiated the neurotoxicity of Aβ. Our data suggest that a humoral immune response to Aβ in AD patients may promote neuronal degeneration, a process with important implications for the future of vaccine-based therapies for AD.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalNeuroMolecular Medicine
Volume3
Issue number1
DOIs
StatePublished - 2003

Keywords

  • Apoptosis
  • Hippocampal
  • Immune
  • Secretase
  • Transgenic

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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