No genetic association between polymorphisms in the Tau gene and Alzheimer's disease in clinic or population based samples

Mutations in the tau protein gene have recently been found to cause familia l fronto-temporal dementia in a number of kindreds demonstrating linkage to chromosome 17. Given that tau pathology is a hallmark of Alzheimer's disea se (AD), this raises the possibility that mutations in tau may also be asso ciated with AD. We have investigated the allelic frequencies of polymorphis ms in the Tau gene for a possible allelic distortion in Alzheimer's cases, which might suggest a conferred genetic risk. We have genotyped 65 communit y-based and 200 clinic-based AD cases, and 142 community-based controls at the Tau exon 6 Afllll and Bsll polymorphisms and find no independent associ ation with risk for AD in these samples. Further analysis including APOE ge notypes from the same samples demonstrated no interaction between either of these polymorphisms and APOE in conferring risk for AD. In addition, haplo type analysis across both sites revealed no difference in haplotype frequen cies between cases and controls, nor any interaction with APOE. Therefore o ur data do not suggest any association between these variations in the Tau gene and Alzheimer's disease. (C) 1999 Elsevier Science Ireland Ltd. All ri ghts reserved.