title: A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease.
abstract: Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Janus
authors.forename: J
authors.initials: J
authors.lastname: Pearson
authors.forename: J
authors.initials: J
authors.lastname: McLaurin
authors.forename: P M
authors.initials: PM
authors.lastname: Mathews
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: S D
authors.initials: SD
authors.lastname: Schmidt
authors.forename: M A
authors.initials: MA
authors.lastname: Chishti
authors.forename: P
authors.initials: P
authors.lastname: Horne
authors.forename: D
authors.initials: D
authors.lastname: Heslin
authors.forename: J
authors.initials: J
authors.lastname: French
authors.forename: H T
authors.initials: HT
authors.lastname: Mount
authors.forename: R A
authors.initials: RA
authors.lastname: Nixon
authors.forename: M
authors.initials: M
authors.lastname: Mercken
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.forename: P
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: D
authors.initials: D
authors.lastname: Westaway
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000517:prevention & control*; D000682:Amyloid / Q000008:administration & dosage; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D058228:Islet Amyloid Polypeptide; D018782:Maze Learning; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage*; D058225:Plaque, Amyloid; D014611:Vaccination
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)