Cribbs DH, David H, Agadjanyan MG.
Immunotherapy for Alzheimer's Disease: Potential Problems and Possible Solutions.
Current Immunology Reviews. 2005 June 1;1(2):139-155.
The primary component of senile plaques is the bgr-amyloid peptide (Abgr), and the amyloid cascade hypothesis proposes that this putative neuropathological peptide is a causal factor in the onset and progression of Alzheimer's disease (AD). Many of the strategies currently being investigated as therapies for AD are aimed at reducing the level of Abgr in the brain or blocking the assembly of the peptide into potentially pathological forms. Immunization of APP/Tg mice with fibrillar Abgr, induced anti-Abgr antibodies, which reduced Ab plaque deposition and neuritic dystrophy, astrogliosis in the brains of APP/Tg mice, and diminished learning deficits in these mice. The first clinical trial was halted, however, when 6% of the participants developed some degree of meningoencephalitis. Preliminary analysis of the first clinical trial has produced some encouraging results including a reduction in plaque load and attenuation of cognitive decline in some vaccinated patients. In this review, we discuss the current status of Abgr-immunotherapy and offer our analysis of the probable cause of the failure of the clinical trial. We believe that the development of safe and effective Abgr-immunotherapy requires selection of an antigen that will induce an adequate anti-Abgr antibody response in the absence of potentially adverse self T cell- mediated events.