The H2 MAPT haplotype is associated with familial frontotemporal dementia.

There is now considerable evidence that the gene encoding for tau protein (MAPT) is implicated in frontotemporal dementia (FTD). The role of MAPT haplotypes in neurodegenerative diseases has been suggested, but their contribution in familial dementia has not been extensively investigated. Here, we investigated (1) the association between the MAPT haplotypes and sporadic (sFTD) or familial FTD (FFTD) (controls n = 99, sFTD n = 53, FFTD n = 50), (2) the interactive effect between MAPT haplotypes and APOE gene. We found an overrepresentation of H2 haplotype (OR = 1.83, P = 0.029) and of H2H2 genotype in FFTD patients (OR = 6.09, P = 0.007). This association was even stronger in APOE e4 negatives FFTD (H2: OR = 2.9, P = 0.001; H2H2: OR = 12.67, P = 0.001). Our results support idea that the MAPT H2 haplotype is a risk factor for FFTD. This locus could contain this or other inheritable genetic determinants contributing to increase risk of developing dementia.