Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2892-7. doi: 10.1073/pnas.050004797.

Abstract

Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (Abeta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Abeta deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Abeta deposition also occurred in APP(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Abeta deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Benzothiazoles
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Hippocampus / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Nerve Degeneration* / pathology
  • Neurites / metabolism*
  • Neurites / pathology
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Protein Isoforms / metabolism*
  • Thiazoles / metabolism
  • Time Factors

Substances

  • Apolipoproteins E
  • Benzothiazoles
  • Protein Isoforms
  • Thiazoles
  • thioflavin T