title: Immunization with amyloid-beta using GM-CSF and IL-4 reduces amyloid burden and alters plaque morphology.
abstract: Alzheimer's disease is a neurodegenerative disease characterized by the formation of plaques composed of amyloid-beta (Abeta) peptide. Vaccination of transgenic models reduced Abeta deposition and protected these mice from memory deficits. However, Phase IIa clinical trials were halted prematurely. Since several investigators have suggested that the adjuvant QS-21 may have promoted the inflammatory response we investigated alternate adjuvants. Our results suggest that GM-CSF and IL-4 drive an attenuated Th2 response to immunization with A, including moderate antibody titers. These antibodies decreased plaque load in transgenic mice by as much as 43%. Total Abeta(40) and Abeta(42) levels were reduced in Abeta/GM-CSF/IL-4 animals, while plasma Abeta(40) and Abeta(42) were increased. Reductions in Abeta resulted in altered plaque morphology. Immunohistochemical analyses show fewer compact deposits composed primarily of Abeta(40) in treated mice, with a concomitant reduction in plaque-associated microgliosis. Thus, GM-CSF and IL-4 are effective adjuvants for Abeta immunotherapy.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: DaSilva
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brown
authors.forename: David
authors.initials: D
authors.lastname: Westaway
authors.forename: JoAnne
authors.initials: J
authors.lastname: McLaurin
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D007114:Immunization; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D058225:Plaque, Amyloid / Q000276:immunology / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor