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.
Department of Physiology, Central South University, Changsha, China.
Songjiang
S
Zhang
Lixiang
L
Wu
Fayi
F
Liu
Bosheng
B
Huang
Dong
D
Huang
Lijuan
L
Yang
Zhihong
Z
Peng
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000917:Antibody Formation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D007106:Immune Sera; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology* / Q000633:toxicity; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D016229:Amyloid beta-Peptides; D007106:Immune Sera; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)