NR AHFG
AU Lesuisse,C.; Xu,G.; Anderson,J.; Wong,M.; Jankowsky,J.; Holtz,G.; Gonzalez,V.; Wong,P.C.; Price,D.L.; Tang,F.; Wagner,S.; Borchelt,D.R.
TI Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice
QU Human Molecular Genetics 2001 Oct 15; 10(22): 2525-37
PT journal article
AB 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.
MH Amyloid beta-Protein/metabolism; Amyloid beta-Protein Precursor/genetics/metabolism; Animal; Apolipoproteins E/genetics/*metabolism; Astrocytes/cytology/*metabolism; Brain/metabolism; Cells, Cultured; Gene Expression Regulation; Human; Immunoblotting; Mice; Mice, Transgenic; Mutation; Neurons/cytology/*metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors
AD Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building-Room 558, Baltimore, MD 21205, USA
SP englisch
PO England