EFFECT OF APOLIPOPROTEIN-E ON NEURITE OUTGROWTH AND BETA-AMYLOID-INDUCED TOXICITY IN DEVELOPING RAT PRIMARY HIPPOCAMPAL CULTURES

The correlation between the epsilon 4 allele of apolipoprotein E (apoE ) and Alzheimer's disease is well established. However, the role of ap oE in normal as well as pathological brain processes remains unclear. We evaluated the effect of apoE treatment on development and beta-amyl oid (A beta)-induced toxicity using primary cultures of developing rat hippocampal neurons. The source of apoE was conditioned media from HE K cells stably transfected with human apoE3 or apoE4 cDNA, a preparati on where apoE is lipid-associated. Morphological and biochemical chang es in the cultures were assessed at 1 and 3 days following low- and hi gh-density plating with either apoE3 or E4 with or without A beta. Bot h apoE isoforms were neurotrophic, as measured by increased neurite le ngth. Aged A beta(1-42), a peptide preparation exhibiting extensive fi bril and aggregate formation, is toxic to these cultures. Addition of apoE3 and E4 significantly and comparably attenuated the A beta-induce d reduction in both neurite length and cell viability. The level of pr otection against this toxicity was proportional to the neurotrophic ac tions of the two apoE isoforms. Thus, apoE acts as a potent growth fac tor in both the absence and the presence of A beta, supporting a poten tially important role for apoE in neurobiology.