title: Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization.
abstract: The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid beta protein (Abeta) can be targeted in a similar manner to animal cell-derived or synthetic Abeta. Because the structure of Abeta depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric Abeta species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains Abeta dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-Abeta monoclonal antibody can prevent this disruption of synaptic plasticity. Abeta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble Abeta oligomers in early Alzheimer's disease.
authors.affiliation: Institute of Neuroscience and Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland.
authors.forename: Igor
authors.initials: I
authors.lastname: Klyubin
authors.forename: Vicki
authors.initials: V
authors.lastname: Betts
authors.forename: Alfred T
authors.initials: AT
authors.lastname: Welzel
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
authors.forename: William K
authors.initials: WK
authors.lastname: Cullen
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: Roger
authors.initials: R
authors.lastname: Anwyl
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rowan
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D017774:Long-Term Potentiation / Q000276:immunology; D008297:Male; D009473:Neuronal Plasticity / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal