Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice

Hum Mol Genet. 2001 Oct 15;10(22):2525-37. doi: 10.1093/hmg/10.22.2525.


Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of A beta deposits. In the present study, we asked whether elevating the levels of Apo E can, in a dominant fashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via the mouse prion protein promoter, resulting in high expression in both astrocytes and neurons; only astrocytes efficiently secreted Hu Apo E4 (at least 5-fold more than endogenous). Mice hyper-expressing Hu Apo E4 developed normally and lived normal lifespans. The co-expression of Hu Apo E4 with a mutant amyloid precursor protein (APP) (Mo/Hu APPswe) or mutant APP and mutant presenilin (PS1dE9) did not lead to proportional changes in the age of appearance, relative burden, character or distribution of A beta deposits. We suggest that these data are best explained by proposing that the mechanisms by which Apo E influences A beta deposition involves an aspect of its normal function that is not augmented by hyper-expression.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Brain / metabolism
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Immunoblotting
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neurons / cytology
  • Neurons / metabolism*
  • Time Factors


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Apolipoprotein E4
  • Apolipoproteins E