Active immunotherapy facilitates Aß plaque removal following through microglial activation without obvious T cells infiltrating the CNS.

ABSTRACT

Immunization of AD mouse models with Aß reduced Aß deposits and improved memory and learning deficits, but some clinical trials of immunization with Aß were halted due to brain inflammation which was presumably induced by a T cell-mediated autoimmune response. We have developed a "possibly safer" vaccine. Our results demonstrate that pcDNA3.1 vector encoding ten repeats of Aß3-10 fragments elicited high titers of antibodies which reacted well with not only monomeric but also oligomeric and fibrillar forms of Aß42 peptide. Induced antibodies strongly reacted with amyloid plaques in the brain, demonstrating functional activity of the antibodies. Immunohistochemical and immunofluorescence showed there was significantly less plaque deposition accomplied with less microglia activation as detected both in the frontal cortex and hippocampus. These data suggested that microglial activation is necessary for efficient removal of compact amyloid deposits with immunotherapy. No obvious inflammation T cell and Prussian blue positive cell was found indicated that inflammation T cell infiltration and microhemmorage can be avoided or at least reduced to the minimum level.