Is there a future for vaccination as a treatment for Alzheimer’s disease?

Vaccination of APP transgenic mice with Aβ has been shown to prevent amyloid deposits. A clinical trial of Aβ 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 Aβ should not produce an autoimmune reaction although this would be anticipated in AD. Moreover, mouse C1q poorly recognizes human Aβ 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.