NO INTERACTION BETWEEN THE APOE AND THE ALPHA-1-ANTICHYMOTRYPSIN GENES ON RISK FOR ALZHEIMERS-DISEASE

It is now known that possession of one of the three common forms of th e apolipoprotein E gene (allele epsilon 4) confers an increased risk f or Alzheimer's disease (AD), both familial and sporadic, and that this risk is dose-dependent. Other genes that may play a role in AD, eithe r through independent association with the disease or through modifica tion of, or interaction with, the existing apolipoprotein E (APOE) ris k, are now under investigation including the alpha-1-antichymotrypsin (ACT) gene, the very low density lipoprotein receptor (VLDL-R) gene, a nd the presenilin-1 (PS-1) gene. Kamboh et al. [1995] reported that a polymorphism in the alpha-1-antichymotrypsin gene could modify the ris k for AD conferred by the APOE locus, specifically by increasing the r isk for AD among epsilon 4 homozygotes. The ACT gene, which is found o n chromosome 14, has previously been proposed as a candidate for AD du e to the presence of the ACT protein in senile plaques and the reporte d elevation of the protein in the cerebro-spinal fluid (CSF) and serum of AD cases. We have investigated this reported association within ou r familial and sporadic AD dataset, where we find no independent assoc iation between ACT and the occurrence of AD, Logistic regression analy sis excludes ACT or the interaction between ACT and APOE as significan t contributors in the prediction of disease status. By this analysis, ACT genotyping does not provide additional information about an indivi dual's risk of Alzheimer's disease beyond the risk information conferr ed by APOE genotype alone. (C) 1997 Wiley-Liss, Inc.