M.A. Marques, M. Tolar and K.A. Crutcher, Apolipoprotein E exhibits
isoform-specific neurotoxicity, Alzheimer's Research, 3:1-6 (1997).
Abstract
A 22 kDa apoE fragment1 and synthetic apoE peptides exhibit neurotoxic effects2 that are receptor-mediated3. In the present study, conditioned medium from apoE-transfected cells and purified apoE were tested for neurotoxicity. The E4 conditioned medium was neurotoxic but contained several lower molecular weight fragments in addition to apoE. Both the E3 and E4 isoforms of purified apoE were also found to cause death of dissociated chick sympathetic neurons in culture, with the E4 isoform being more toxic than the E3 isoform. However, medium collected from cultures to which purified apoE had been added was found to contain a lower molecular weight fragment (approx. m.w. = 22 kDa). Since the 22 kDa thrombin cleavage fragment of apoE has been shown to exhibit isoform-specific neurotoxicity, these results suggest that the neurotoxic effect of apoE may be due to the generation of a similar fragment in vitro. These findings provide additional support for the hypothesis that apoE plays a direct role in the neuropathology of Alzheimer's disease.
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