Mutations in the tau protein gene have recently been found to cause familial fronto-temporal dementia in a number of kindreds demonstrating linkage to chromosome 17. Given that tau pathology is a hallmark of Alzheimer's disease (AD), this raises the possibility that mutations in tau may also be associated with AD. We have investigated the allelic frequencies of polymorphisms in the Tau gene for a possible allelic distortion in Alzheimer's cases, which might suggest a conferred genetic risk. We have genotyped 65 community-based and 200 clinic-based AD cases, and 142 community-based controls at the Tau exon 6 AflIII and BslI polymorphisms and find no independent association with risk for AD in these samples. Further analysis including APOE genotypes from the same samples demonstrated no interaction between either of these polymorphisms and APOE in conferring risk for AD. In addition, haplotype analysis across both sites revealed no difference in haplotype frequencies between cases and controls, nor any interaction with APOE. Therefore our data do not suggest any association between these variations in the Tau gene and Alzheimer's disease.