C. Lesuisse et al., Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice, HUM MOL GEN, 10(22), 2001, pp. 2525-2537
Recent studies in mice have clearly demonstrated that eliminating Apo E alt
ers 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 f
ashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via th
e mouse prion protein promoter, resulting in high expression in both astroc
ytes and neurons; only astrocytes efficiently secreted Hu Apo E4 (at least
5-fold more than endogenous). Mice hyper-expressing Hu Apo E4 developed nor
mally and lived normal lifespans. The co-expression of Hu Apo E4 with a mut
ant amyloid precursor protein (APP) (Mo/Hu APPswe) or mutant APP and mutant
presenilin (PS1dE9) did not lead to proportional changes in the age of app
earance, 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 norm
al function that is not augmented by hyper-expression.