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

Christian Lesuisse, Guilian Xu, Jeffery Anderson, Molly Wong, Joanna Jankowsky, Greg Holtz, Victoria Gonzalez, Philip C.Y. Wong, Donald L. Price, Fai Tang, Steve Wagner, David R. Borchelt

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of Aβ 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 Aβ deposits. We suggest that these data are best explained by proposing that the mechanisms by which Apo E influences Aβ deposition involves an aspect of its normal function that is not augmented by hyper-expression.

Original languageEnglish (US)
Pages (from-to)2525-2537
Number of pages13
JournalHuman molecular genetics
Volume10
Issue number22
DOIs
StatePublished - Oct 15 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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