Intramembranous fragment of amyloid-beta: 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-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.