title: Active immunotherapy facilitates Aβ plaque removal following through microglial activation without obvious T cells infiltrating the CNS.
abstract: Immunization of AD mouse models with Aβ reduced Aβ deposits and improved memory and learning deficits, but some clinical trials of immunization with Aβ 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 Aβ3-10 fragments elicited high titers of antibodies which reacted well with not only monomeric but also oligomeric and fibrillar forms of Aβ42 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.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liao Ning Province, China. Electronic address: yanbingxingya@163.com.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.affiliation: Department of Neurology, Provincial People's Hospital, Shenyang 110001, Liao Ning Province, China.
authors.forename: Xiao-Na
authors.initials: XN
authors.lastname: Xing
authors.affiliation: Department of Neurology, the First Affiliated Hospital of China Medical University, China. Electronic address: ypengcao@yahoo.com.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Cao
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology; D002543:Cerebral Hemorrhage / Q000276:immunology / Q000628:therapy; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology / Q000628:therapy*; D016233:Immunotherapy, Active / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000276:immunology / Q000628:therapy*; D011897:Random Allocation; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019444:Vaccines, DNA; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid β-protein; Microglial; T cell infiltration