Neurite Degeneration Elicited by Apolipoprotein E Peptides

Apolipoprotein E (apoE) has been localized to the neurofibrillary tangles and β-amyloid-containing plaques found in the cortex of patients with Alzheimer's disease (AD) (14, 28), suggesting that apoE may play a role in this disorder. Recently, synthetic peptides containing a sequence within apoE (amino acids 141-155) were found to be cytotoxic to T lymphocytes in culture. In the present study, tandem presentation of the apoE sequence E141-155, as well as longer monomeric peptides that include this domain, was found to cause extensive and specific degeneration of neurites from embryonic chick sympathetic ganglia in vitro. These results, together with the observation of strong βA4/apoE binding in vitro and the disproportionate occurrence of the ϵ4 allele in both familial and sporadic AD patients, suggest that peptide sequences associated with apoE may contribute directly to neurodegenerative processes.