PLoS ONE (Apr 2011)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0019338
Journal volume & issue
Vol. 6, no. 4
p. e19338

Abstract

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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.