Fig. 1.

ApoE neurotoxicity may involve proteolysis. Dissociated chick sympathetic neurons were exposed to the apoE peptide (ApoE_p) or full-length apoE4 (apoE4) in the presence or absence of protease inhibitors (PI). Controls included cells not receiving any experimental treatment (Control), receiving protease inhibitors alone (PI), or treated with an antibody against mouse IgG (IgG) that had been subjected to the same purification procedure as that used for apoE4. Significant toxicity was obtained with the apoE peptide and apoE4 but not with the control treatments. Protease inhibitors prevented the toxic effects of apoE4 but not of the apoE peptide. Medium from the cultures treated with apoE4 with or without PI was subjected to Western blotting using an antibody to apoE. The results are shown below the corresponding treatments in the bar graph. PI treatment reduced the number and intensity of bands representing low molecular weight apoE fragments in the medium. The approximate location of the molecular weight standards is indicated to the left of the Western blot.