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Intramembranous fragment of amyloid-beta: A potential immunogen for Alzheimer's disease immunotherapy.

Abstract
Immunotherapy holds great promise for Alzheimer's disease (AD), but meningoencephalitis observed in the first AD vaccination trial, which accompanied T-lymphocytic infiltration, needs to be overcome. This study was aimed to investigate alternative approaches for a safer vaccine to treat AD. We used intramembranous fragment of amyloid-beta (IF-Abeta) to immunize Kunming mice for up to 2.5 months and then evaluated the immunization efficacy and potential adverse effects. Immunization of mice with IF-Abeta plus Freund's adjuvant resulted in moderate levels of Abeta antibodies (IgG), and the anti-sera were able to neutralize Abeta1-42-neurotoxicity in cultured primary cortical neurons. IF-Abeta itself did not show neurotoxicity, and immunization with IF-Abeta did not cause behavioral deficits in Morris water maze or any abnormalities by histological examinations of major organs including the brain. We conclude that vaccination with IF-Abeta may be a potentially safe and effective treatment for AD.
AuthorsSongjiang Zhang, Lixiang Wu, Fayi Liu, Bosheng Huang, Dong Huang, Lijuan Yang, Zhihong Peng
JournalNeurochemical research (Neurochem Res) Vol. 34 Issue 11 Pg. 1889-95 (Nov 2009) ISSN: 1573-6903 [Electronic] United States
PMID19347579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amyloid beta-Peptides
  • Immune Sera
  • Immunoglobulin G
  • Peptide Fragments
  • amyloid beta-protein (1-42)
Topics
  • Alzheimer Disease (immunology, therapy)
  • Amyloid beta-Peptides (immunology, toxicity)
  • Animals
  • Antibody Formation
  • Cells, Cultured
  • Cerebral Cortex (drug effects, pathology)
  • Immune Sera
  • Immunoglobulin G (blood)
  • Immunotherapy
  • Kidney (drug effects, pathology)
  • Liver (drug effects, pathology)
  • Male
  • Maze Learning (drug effects)
  • Memory (drug effects)
  • Mice
  • Neurons (drug effects, pathology)
  • Peptide Fragments (adverse effects, immunology, toxicity)
  • Spleen (drug effects, pathology)

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