Intramembranous Fragment of Amyloid-β: A Potential Immunogen for Alzheimer's Disease Immunotherapy

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-A beta) 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-A beta plus Freund's adjuvant resulted in moderate levels of A beta antibodies (IgG), and the anti-sera were able to neutralize A beta 1-42-neurotoxicity in cultured primary cortical neurons. IF-A beta itself did not show neurotoxicity, and immunization with IF-A beta 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-A beta may be a potentially safe and effective treatment for AD.