title: Beta-amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer's disease.
abstract: Alzheimer's disease neuropathology is characterized by key features that include the deposition of the amyloid beta peptide (Abeta) into plaques, the formation of neurofibrillary tangles, and the loss of neurons and synapses in specific brain regions. The loss of synapses, and particularly the associated presynaptic vesicle protein synaptophysin in the hippocampus and association cortices, has been widely reported to be one of the most robust correlates of Alzheimer's disease-associated cognitive decline. The beta-amyloid hypothesis supports the idea that Abeta is the cause of these pathologies. However, the hypothesis is still controversial, in part because the direct role of Abeta in synaptic degeneration awaits confirmation. In this study, we show that Abeta reduction by active or passive Abeta immunization protects against the progressive loss of synaptophysin in the hippocampal molecular layer and frontal neocortex of a transgenic mouse model of Alzheimer's disease. These results, substantiated by quantitative electron microscopic analysis of synaptic densities, strongly support a direct causative role of Abeta in the synaptic degeneration seen in Alzheimer's disease and strengthen the potential of Abeta immunotherapy as a treatment approach for this disease.
authors.affiliation: Elan Pharmaceuticals, South San Francisco, California 94080, USA. manuel.buttini@elan.com
authors.forename: Manuel
authors.initials: M
authors.lastname: Buttini
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Robin
authors.initials: R
authors.lastname: Barbour
authors.forename: Henry
authors.initials: H
authors.lastname: Grajeda
authors.forename: Ruth
authors.initials: R
authors.lastname: Motter
authors.forename: Kelly
authors.initials: K
authors.lastname: Johnson-Wood
authors.forename: Karen
authors.initials: K
authors.lastname: Khan
authors.forename: Peter
authors.initials: P
authors.lastname: Seubert
authors.forename: Stephen
authors.initials: S
authors.lastname: Freedman
authors.forename: Dale
authors.initials: D
authors.lastname: Schenk
authors.forename: Dora
authors.initials: D
authors.lastname: Games
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013569:Synapses / Q000187:drug effects*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D016708:Synaptophysin