A Beta Peptide Immunization Reduces Behavioural Impairment and Plaques in a Model of Alzheimer's Disease

Nature. 2000 Dec 21-28;408(6815):979-82. doi: 10.1038/35050110.

Abstract

Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control*
  • Amyloid / administration & dosage
  • Amyloid beta-Peptides / administration & dosage*
  • Animals
  • Cricetinae
  • Disease Models, Animal
  • Hippocampus / pathology
  • Humans
  • Islet Amyloid Polypeptide
  • Maze Learning
  • Mesocricetus
  • Mice
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Peptide Fragments / administration & dosage*
  • Plaque, Amyloid
  • Vaccination*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Islet Amyloid Polypeptide
  • Peptide Fragments
  • amyloid beta-protein (1-42)