Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation

Nat Med. 2004 Nov;10(11):1190-2. doi: 10.1038/nm1123. Epub 2004 Oct 24.

Abstract

The Arctic mutation within the amyloid-beta (Abeta) peptide causes Alzheimer disease. In vitro, Arctic-mutant Abeta forms (proto)fibrils more effectively than wild-type Abeta. We generated transgenic mouse lines expressing Arctic-mutant human amyloid precursor proteins (hAPP). Amyloid plaques formed faster and were more extensive in Arctic mice than in hAPP mice expressing wild-type Abeta, even though Arctic mice had lower Abeta(1-42/1-40) ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Hippocampus / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics*
  • Plaque, Amyloid / metabolism*

Substances

  • Amyloid beta-Protein Precursor