It is now known that possession of one of the three common forms of the 
apolipoprotein E gene (allele epsilon 4) confers an increased risk for 
Alzheimer's disease (AD), both familial and sporadic, and that this risk is 
dose-dependent. Other genes that may play a role in AD, either through 
independent association with the disease or through modification of, or 
interaction with, the existing apolipoprotein E (APOE) risk, are now under 
investigation including the alpha-1-antichymotrypsin (ACT) gene, the very low 
density lipoprotein receptor (VLDL-R) gene, and the presenilin-1 (PS-1) gene. 
Kamboh et al. [1995] reported that a polymorphism in the 
alpha-1-antichymotrypsin gene could modify the risk for AD conferred by the APOE 
locus, specifically by increasing the risk for AD among epsilon 4 homozygotes. 
The ACT gene, which is found on chromosome 14, has previously been proposed as a 
candidate for AD due to the presence of the ACT protein in senile plaques and 
the reported elevation of the protein in the cerebro-spinal fluid (CSF) and 
serum of AD cases. We have investigated this reported association within our 
familial and sporadic AD dataset, where we find no independent association 
between ACT and the occurrence of AD. Logistic regression analysis excludes ACT 
or the interaction between ACT and APOE as significant contributors in the 
prediction of disease status. By this analysis, ACT genotyping does not provide 
additional information about an individual's risk of Alzheimer's disease beyond 
the risk information conferred by APOE genotype alone.