Association between tau polymorphism and male early-onset Alzheimer's disease

Neurofibrillary tangles, containing hyperphosphorylated microtubule-associated protein tau, are one of the major pathological hallmarks of Alzheimer's disease. To investigate a possible association between tau genotypes and the risk of Alzheimer's disease, we screened for polymorphisms in the tau gene and found a novel polymorphism IVS11 + 90G --> A. A case-control study (874 patients and 678 controls) showed a significant association between possession of the A allele and male Alzheimer's disease with early-onset (age of onset before 65, odds ratio = 2.65; 95% confidence interval 1.30-5.42), suggesting that age and gender modify the risk effect. However, we failed to replicate the reported association between the Saitohin gene located in the tau intron 9 and Japanese Alzheimer's disease.