title: Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease.
abstract: Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB.
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, California, United States of America. emasliah@ucsd.edu
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.forename: Leslie
authors.initials: L
authors.lastname: Crews
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.forename: Christina
authors.initials: C
authors.lastname: Patrick
authors.forename: Margarita
authors.initials: M
authors.lastname: Trejo
authors.forename: Kiren
authors.initials: K
authors.lastname: Ubhi
authors.forename: Troy T
authors.initials: TT
authors.lastname: Rohn
authors.forename: Sarah
authors.initials: S
authors.lastname: Mueller-Steiner
authors.forename: Peter
authors.initials: P
authors.lastname: Seubert
authors.forename: Robin
authors.initials: R
authors.lastname: Barbour
authors.forename: Lisa
authors.initials: L
authors.lastname: McConlogue
authors.forename: Manuel
authors.initials: M
authors.lastname: Buttini
authors.forename: Dora
authors.initials: D
authors.lastname: Games
authors.forename: Dale
authors.initials: D
authors.lastname: Schenk
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001522:Behavior, Animal; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D007116:Immunization, Passive / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods; D020961:Lewy Body Disease / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D008247:Lysosomes / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology; D051381:Rats; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D051844:alpha-Synuclein