Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid β-peptide deposition in homozygous APP(V717F) transgenic mice

Michael C. Irizarry, Bonnie S. Cheung, G. William Rebeck, Steven M. Paul, Kelly R. Bales, B. T. Hyman

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Apolipoprotein E (apoE) has been implicated as a risk factor for Alzheimer's disease and in the deposition, fibrillogenesis, and clearance of the amyloid β-peptide (Aβ). To examine the in vivo interactions between apoE and Aβ deposition, we examined 12-month-old transgenic (tg) mice expressing human amyloid precursor protein (APP) with the V717F mutation (APP(V717F) homozygous) on an APOE null background. Elimination of APOE resulted in a redistribution and alteration in the character of Aβ deposition in homozygous APP(V717F) tg mice, with a dramatic reduction in cortical and dentate gyrus deposition, prominent increase in diffuse CA1 and CA3 deposition, and prevention of the formation of thioflavin-S-positive deposits. These alterations in Aβ deposition were not mediated by significant changes in regional APP expression, low-density lipoprotein receptor-related protein expression, or soluble Aβ levels. Thus, apoE in APP(V717F) tg mice not only affects the amount and form of Aβ deposition, but also the anatomical distribution of diffuse Aβ deposits. The APP(V717F) tg mouse can serve as a model to investigate genetic influences on the vulnerability of specific neuroanatomical regions to Aβ deposition.

Original languageEnglish
Pages (from-to)451-458
Number of pages8
JournalActa Neuropathologica
Volume100
Issue number5
DOIs
StatePublished - 2000

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Apolipoprotein E
  • Hippocampus
  • Transgenic mice

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