Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease.

by: Eliezer Masliah, Edward Rockenstein, Michael Mante, Leslie Crews, Brian Spencer, Anthony Adame, Christina Patrick, Margarita Trejo, Kiren Ubhi, Troy T Rohn, Sarah Mueller-Steiner, Peter Seubert, Robin Barbour, Lisa McConlogue, Manuel Buttini, Dora Games, Dale Schenk

Format: Article
Published: Public Library of Science (PLoS) 2011-04-01

Description

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.