De novo induction of amyloid-β deposition in vivo

Mol Psychiatry. 2012 Dec;17(12):1347-53. doi: 10.1038/mp.2011.120. Epub 2011 Oct 4.

Abstract

Alzheimer's disease (AD), the most common type of senile dementia, is associated to the build-up of misfolded amyloid-β (Aβ) in the brain. Although compelling evidences indicate that the misfolding and oligomerization of Aβ is the triggering event in AD, the mechanisms responsible for the initiation of Aβ accumulation are unknown. In this study, we show that Aβ deposition can be induced by injection of AD brain extracts into animals, which, without exposure to this material, will never develop these alterations. The accumulation of Aβ deposits increased progressively with the time after inoculation, and the Aβ lesions were observed in brain areas far from the injection site. Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Disease Models, Animal*
  • Female
  • Hippocampus / metabolism*
  • Humans
  • Infant
  • Male
  • Mice
  • Mice, Transgenic
  • Microinjections
  • Protein Folding
  • Tissue Extracts / administration & dosage
  • Tissue Extracts / adverse effects*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Tissue Extracts