The E4 allele for the apolipoprotein E gene has been shown to be a significant risk factor for Alzheimer's disease. The gene is located in a conserved gene cluster on chromosome 19q12-13.2. Downstream from APOE is the gene for apolipoprotein CI. We had previously shown that the presence of a restriction site in the 5′end of APOCI (the A allele) was present at increased frequency in Alzheimer's patients and could also be considered as a risk factor for the disease. We have extended these studies and find that both familial and sporadic cases of Alzheimer's disease have a higher frequency of the APOCI A allele than control spouses. In addition, male patients with the APOCI A allele and/or the APOE4 allele tend to have an earlier age of onset of the disease than female patients.