Increased risk for frontotemporal dementia through interaction between tau polymorphisms and apolipoprotein E ε4

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Abstract
The tau gene has an important role in frontotemporal dementia (FTD) as pathogenic mutations have been found in hereditary forms of the disease. Furthermore, a certain extended tau haplotype has been shown to increase the risk for progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease and, in interaction with the apolipoprotein E (apoE) ∊4 allele, Alzheimer's disease. By microsatellite analysis we investigated an intronic tau polymorphism, in linkage disequilibrium with the extended tau haplotype, in FTD patients (n = 36) and healthy controls (n = 39). No association between any of the tau alleles/genotypes and FTD was seen, but certain tau alleles and apoE ∊4 interactively increased the risk of FTD (p = 0.006). We thus propose that this extended tau haplotype in combination with apoE ∊4 is a genetic risk factor for FTD.