Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains

Brain Res. 2011 Jan 12;1368:239-47. doi: 10.1016/j.brainres.2010.10.053. Epub 2010 Oct 21.

Abstract

Inflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Overexpression of tumor necrosis factor-α (TNF-α) occurs in the AD brain. Recent clinical studies have shown that the anti-TNF-α therapy improves cognition function of AD patients rapidly. However, the underlying mechanism remains elusive. The present study investigates the effects of intracerebroventricular injection of the monoclonal TNF-α antibody, Infliximab, on the pathological features of AD in the APP/PS1 double transgenic mice. We found that Infliximab administration reduced the levels of TNF-α, amyloid plaques, and tau phosphorylation as early as three days after daily injection of 150 μg Infliximab for three days. The number of CD11c-positive dendritic-like cells and the expression of CD11c were found to be increased concurrently after Infliximab injection. These data suggested that the CD11c-positive dendritic-like cells might contribute to the Infliximab-induced reduction of AD-like pathology. Furthermore, our results support the use of anti-TNF-α for the treatment of AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / immunology
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Brain / drug effects
  • Brain / metabolism*
  • CD11c Antigen / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Infliximab
  • Injections, Intraventricular
  • Mice
  • Mice, Transgenic
  • Phosphorylation / drug effects
  • Plaque, Amyloid / drug therapy
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology*
  • tau Proteins / metabolism

Substances

  • Antibodies, Monoclonal
  • CD11c Antigen
  • Tumor Necrosis Factor-alpha
  • tau Proteins
  • Infliximab