Immunization of Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH vaccine prevents synaptic deficits of Alzheimer's disease

Behav Brain Res. 2017 Aug 14:332:64-70. doi: 10.1016/j.bbr.2017.05.056. Epub 2017 May 31.

Abstract

The amyloid cascade hypothesis is widely accepted by researchers as the mechanism of Alzheimer's disease. Active immunization to eliminate Aβ depositions has been used in preclinical and clinical studies. Aβ3-10-KLH is a vaccine of the Aβ3-10 peptide combined with keyhole limpet hemocyanin (KLH). We immunized 2.5-month-old Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH peptide and Aβ1-42 peptide to eliminate Aβ deposits in the brains of these transgenic mice. The results of immunohistochemical staining and transmission electron microscopy detection indicated that our new vaccine was more advantageous in protecting synaptic function and structure than the Aβ1-42 peptide. Aβ3-10-KLH peptide is an effective vaccine in the treatment of Alzheimer's disease.

Keywords: Alzheimer’s disease; Amyloid-β-peptide; Aβ3-10-KLH vaccine; Cognitive deficit; Synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / therapy*
  • Alzheimer Vaccines / administration & dosage*
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / immunology*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cerebral Cortex / immunology
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Hemocyanins / immunology
  • Hippocampus / immunology
  • Hippocampus / pathology
  • Humans
  • Immunohistochemistry
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology*
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / therapy
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Random Allocation
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / pathology*
  • Synaptophysin / metabolism
  • Vaccination

Substances

  • APP protein, human
  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • NR2B NMDA receptor
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • Receptors, N-Methyl-D-Aspartate
  • Synaptophysin
  • Syp protein, mouse
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (3-10)
  • Hemocyanins
  • keyhole-limpet hemocyanin