DNA Aβ42 Vaccination as Possible Alternative Immunotherapy for Alzheimer Disease

Abstract

Immunotherapy for Alzheimer disease was advanced in reports1,2 showing that the use of Aβ42 peptide vaccination in a transgenic mouse model of Alzheimer disease significantly reduced the Aβ42 plaque count, significantly reduced levels of gliosis, and significantly improved behavior. Based on the positive experimental animal model data, a human Aβ42 peptide immunization clinical trial [ie, the AN1792(QS-21)-201 trial]3 for patients with Alzheimer disease was conducted; however, it was stopped owing to significant adverse effects in 6% of immunized patients. Subsequent studies showed that there were significant reductions in Aβ42-containing plaque in the brain but that the patients continued to become more demented.4 For patients with mild Alzheimer disease, the use of passive immunotherapy with the humanized monoclonal antibody bapineuzumab resulted in no significant clinical benefit, but the use of passive immunotherapy with the humanized monoclonal antibody solanezumab resulted in some memory and behavioral benefits (New York Times, July 24, 2012). Intravenous immunoglobulins, which probably contain anti-Aβ antibodies, have also been used to treat patients with Alzheimer disease, and their use has resulted in clinical stabilization.5