Combined treatment of Aβ immunization with statin in a mouse model of Alzheimer's disease

J Neuroimmunol. 2012 Mar;244(1-2):70-83. doi: 10.1016/j.jneuroim.2012.01.008. Epub 2012 Feb 11.

Abstract

We evaluated the therapeutic efficacy of combined treatment of Aβ-immunization with simvastatin in an Alzheimer mouse model at age 22 months. DNA prime-adenovirus boost immunization induced modest anti-Aβ titers and simvastatin increased the seropositive rate. Aβ-KLH was additionally administered to boost the titers. Irrespective of simvastatin, the immunization did not decrease cerebral Aβ deposits but increased soluble Aβ and tended to exacerbate amyloid angiopathy in the hippocampus. The immunization increased cerebral invasion of leukocytes and simvastatin counteracted the increase. Thus, modest anti-Aβ titers can increase soluble Aβ and simvastatin may reduce inflammation associated with vaccination in aged Alzheimer mouse models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / immunology
  • Alzheimer Disease / prevention & control
  • Alzheimer Vaccines / immunology*
  • Alzheimer Vaccines / therapeutic use
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Cerebral Amyloid Angiopathy / drug therapy
  • Cerebral Amyloid Angiopathy / immunology
  • Cerebral Amyloid Angiopathy / prevention & control
  • Disease Models, Animal
  • Female
  • Hippocampus / drug effects
  • Hippocampus / immunology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Simvastatin / therapeutic use*

Substances

  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin

Supplementary concepts

  • Amyloid angiopathy