Differential neurotrophic effects of apolipoprotein E in aged transgenic mice

The present study seeked to determine whether the neurodegenerative and cog nitive alterations in aged apolipoprotein E-deficient mice are differential ly reversed by transgenic overexpression of human apolipoprotein-E3 vs. apo lipoprotein-E4 in the background of deficient endogenous apolipoprotein E. These studies showed dendritic alterations in pyramidal neurons of apolipop rotein-E4 transgenic mice, similar to the ones observed in apolipoprotein E -deficient mice. However, these mice had a preserved density of synaptophys in-immunoreactive presynaptic terminals. In contrast, mice overexpressing a polipoprotein-E3 showed no synapto-dendritic alterations. Analysis of behav ioral performance in the Morris water maze showed that while apolipoprotein E-deficient mice performed poorly, overexpression of apolipoprotein-E3 and , to a lower extent apolipoprotein-E4, resulted in an improved performance. This study supports the contention that, com pared with apolipoprotein-E4, apolipoprotein-E3 might have a greater neurotrophic in vivo effect in aged mice. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reser ved.