Naturally occurring autoantibodies interfere with β-amyloid metabolism and improve cognition in a transgenic mouse model of Alzheimer's disease 24 h after single treatment

Transl Psychiatry. 2013 Mar 5;3(3):e236. doi: 10.1038/tp.2012.151.

Abstract

There is evidence that naturally occurring antibodies directed against Aβ (nAbs-Aβ) have a role in Aβ-metabolism and Aβ-clearance. The presence of nAbs-Aβ leads to a reduction in amyloid fibrillation and thus a reduction in their toxicity. We investigated the effects of nAbs-Aβ in respect to oligomerization and used the Tg2576 transgenic mouse model in order to investigate the rapid effect with a single-dose (24 h) on oligomer breakdown and cytokine secretion along with immunohistochemical characterization of synaptic plasticity. nAbs-Aβ were able to reduce toxic oligomer concentration with an increase in Aβ-monomers. Cytokine secretion was significantly reduced. Synaptic plasticity was also improved after administration of nAbs. Finally, single treatment lead to a significant improvement in cognition. This study demonstrates the efficacy of nAbs-Aβ and presents evidence that several hallmarks of the disease are targeted by nAbs-Aβ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Autoantibodies / metabolism
  • Autoantibodies / pharmacology*
  • Blotting, Western / methods
  • Cognition / physiology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Mice
  • Mice, Transgenic

Substances

  • Amyloid beta-Peptides
  • Autoantibodies
  • Cytokines