Apolipoprotein E (ApoE)-epsilon 4 allele has been associated with late onset familial Alzheimer's disease (AD). In both familial and sporadic AD brain, ApoE is localized to the vessel walls, senile amyloid plaques, and neurofibrillary tangles. ApoE is also an 'injury-response' macromolecule in peripheral nerves and was reported to increase in response to injury. We have demonstrated that Alzheimer beta-amyloid precursor protein and a serpin alpha 1-antichymotrypsin also found accumulated in senile plaques in AD brain, were also localized at neuromuscular junctions (NMJs). Using immunocytochemistry, our present results indicate that ApoE is found in normal mouse, rat and human skeletal muscle and concentrated at the NMJs as it is in the senile plaques in AD brain. Such experiments may shed light on the mechanism of synapse loss, as well as plaque formation in this neurodegenerative disease.