NEURITE DEGENERATION ELICITED BY APOLIPOPROTEIN-E PEPTIDES

Apolipoprotein E (apoE) has been localized to the neurofibrillary tang les and beta-amyloid-containing plaques found in the cortex of patient s with Alzheimer's disease (AD) (14, 28), suggesting that apoE may pla y a role in this disorder. Recently, synthetic peptides containing a s equence within apoE (amino acids 141-155) were found to be cytotoxic t o T lymphocytes in culture. In the present study, tandem presentation of the apoE sequence E(141-155), as well as longer monomeric peptides that include this domain, was found to cause extensive and specific de generation of neurites from embryonic chick sympathetic ganglia in vit ro. These results, together with the observation of strong beta AB/apo E binding in vitro and the disproportionate occurrence of the epsilon 4 allele in both familial and sporadic AD patients, suggest that pepti de sequences associated with apoE may contribute directly to neurodege nerative processes. (C) 1994 Academic Press, Inc.