Loss of deep cerebellar nuclei neurons in the 3xTg-AD mice and protection by an anti-amyloid β antibody fragment

MAbs. 2013 Sep-Oct;5(5):660-4. doi: 10.4161/mabs.25428. Epub 2013 Jun 20.

Abstract

The therapeutic potential of scFv-h3D6 has recently been shown in the 3xTg-AD mice. A clear effect on amyloid β (Aβ) oligomers and certain apolipoproteins in the brain was found, but no effect was seen in the cerebellum. Here, cellular vulnerability of the 3xTg-AD cerebellum is described for the first time, together with its protection by scFv-h3D6. Neuron depletion in the DCN was regionally variable and followed a mediolateral axis of involvement that was greatest in the fastigial nucleus, lesser in the interpositus and negligible in the dentate nucleus. A sole and low intraperitoneal dose of scFv-h3D6 protected 3xTg-AD DCN neurons from death. Further studies might provide interesting information about both the potential of scFv-h3D6 as a therapeutic agent and the role of the cerebellum in AD.

Keywords: Alzheimer disease; DCN neurons; cerebellum; immunotherapy; scFv-h3D6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / immunology*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cell Count
  • Cell Survival / drug effects
  • Cerebellar Nuclei / drug effects*
  • Cerebellar Nuclei / metabolism
  • Cerebellar Nuclei / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Single-Chain Antibodies / immunology
  • Single-Chain Antibodies / pharmacology*
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Single-Chain Antibodies
  • tau Proteins