An Aβ3-10-KLH vaccine reduced Alzheimer's disease-like pathology and had a sustained effect in Tg-APPswe/PSEN1dE9 mice

Brain Res. 2017 Oct 15:1673:72-77. doi: 10.1016/j.brainres.2017.07.017. Epub 2017 Aug 2.

Abstract

Alzheimer's disease is a neurodegenerative disease that affects many patients worldwide. The amyloid cascade hypothesis has been adopted by most researchers as the mechanism underlying Alzheimer's disease. Aβ plaques have been considered the core factor in the neurotoxic effect in Alzheimer's disease, though some controversy remains. Further effort is necessary to elucidate the mechanism and to develop effective treatments. Previous studies have indicated that eliminating Aβ plaques could improve synaptic plasticity and cognitive function. Researchers have developed various forms of vaccines to prevent Aβ deposition or eliminate Aβ plaques and have made some progress. We developed a new vaccine, Aβ3-10-KLH, to increase the level of the anti-Aβ immune response, and we show that this vaccine resulted in a sustained prevention of Aβ deposition at 4 months after cessation of the vaccine treatment. At the same time point, the expression of synaptophysin and NMDAR2B in APP/PS1 transgenic mice was increased by immunization.

Keywords: Alzheimer’s disease; Aβ plaque; Aβ3-10-KLH vaccine; NMDAR2B; Synaptophysin.

MeSH terms

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

Substances

  • APP protein, human
  • Abeta3-10-KLH vaccine
  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • NR2B NMDA receptor
  • PSEN1 protein, human
  • Presenilin-1
  • Receptors, N-Methyl-D-Aspartate
  • Synaptophysin
  • Syp protein, mouse
  • Vaccines