The effect of tau genotype on clinical features in FTDP-17

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTFDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (HI) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, + 16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between HUM and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the HUM genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR = 11.7; 95% confidence interval, 1.4-98.7; P = 0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17. (c) 2005 Elsevier Ltd. All rights reserved.