E4e4 -apo-e is a cholesterol-carrying protein produced in the liver and brain that circulates in the plasma. it binds to beta-amyloid and becomes incorporated inot neuritic plaques. having 2 alleles for e4, and to a lesser degree having one allele for e4, is associated with an unequivocally increased risk of developing alzheimers disease. risk is accentuated by other factors, such as being older than 80 years, having downs syndrome, or having repeated head injuries. overall, having one e4 allele triples the risk of devloping ad by 80 years, and ahving 2 e4 alleles raises the risk to 90%. an e4 allele is found in more than 50% of ad patients. moreover, ad patients who are apo-e4 homozygous, compared to those who are not, tend to develop ad at an earlier age, experience more rapid decline, and, have greater amyloid content and lower acetycholine activity.