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

PLoS One. 2011 Apr 29;6(4):e19338. doi: 10.1371/journal.pone.0019338.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Behavior, Animal
  • Cell Line, Tumor
  • Disease Models, Animal
  • Immunization, Passive / methods*
  • Immunohistochemistry / methods
  • Lewy Body Disease / genetics*
  • Lewy Body Disease / immunology
  • Lewy Body Disease / therapy*
  • Lysosomes / metabolism
  • Maze Learning
  • Mice
  • Mice, Transgenic
  • Nerve Degeneration / pathology
  • Rats
  • alpha-Synuclein / genetics*

Substances

  • Antibodies, Monoclonal
  • alpha-Synuclein