Is there a future for vaccination as a treatment for Alzheimer's disease?
Vaccination of APP transgenic mice with Abeta has been shown to prevent amyloid deposits. A clinical trial of Abeta vaccination in Alzheimer's disease (AD) was halted due to serious neurological complications developing in some patients. Such complications were not observed in transgenic mice. Since human APP is not a mouse self-protein, vaccination of mice with Abeta should not produce an autoimmune reaction although this would be anticipated in AD. Moreover, mouse C1q poorly recognizes human Abeta so complement activation is much weaker in transgenic mice than in AD. Vaccination will increase complement activation through formation of antigen-antibody complexes. In mice this will enhance phagocytosis. But in AD, where complement is already overactivated, and where the senile plaques are relatively insoluble, this stimulation should increase production of the membrane attack complex, adding to the autodestruction of neurons. The future of vaccination as a therapy for AD will require surmounting the problems of autoimmune reactions generally and autotoxic complement activation specifically.
McGeer
Patrick L
PL
Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, BC, V6T 1Z3, Vancouver, Canada. mcgreerpl@interchange.ubc.ca
McGeer
Edith
E
D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology; D000818:Animals; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology; D014611:Vaccination
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor