Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer's disease Aβ synaptotoxicity

J Neurosci. 2014 Apr 30;34(18):6140-5. doi: 10.1523/JNEUROSCI.3526-13.2014.

Abstract

Alzheimer's disease (AD) is associated with pathological assembly states of amyloid-β protein (Aβ). Aβ-related synaptotoxicity can be blocked by anti-prion protein (PrP) antibodies, potentially allowing therapeutic targeting of this aspect of AD neuropathogenesis. Here, we show that intravascular administration of a high-affinity humanized anti-PrP antibody to rats can prevent the plasticity-disrupting effects induced by exposure to soluble AD brain extract. These results provide an in vivo proof of principle for such a therapeutic strategy.

Keywords: Alzheimer's; drug discovery; immunotherapy; long-term potentiation; prion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / pharmacology*
  • Analysis of Variance
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Biophysics
  • CA1 Region, Hippocampal / drug effects*
  • Drug Administration Routes
  • Electric Stimulation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Long-Term Potentiation / drug effects*
  • Male
  • Peptide Fragments / pharmacology*
  • Prions / immunology*
  • Prions / metabolism
  • Rats
  • Rats, Wistar
  • Temporal Lobe / chemistry
  • Temporal Lobe / metabolism

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal
  • Peptide Fragments
  • Prions
  • amyloid beta-protein (1-42)