BACKGROUND: The frontotemporal dementia (FTD) syndromes have been associated with the microtubule-associated tau protein since tau gene mutations have been demonstrated to be the cause of FTD and parkinsonism linked to chromosome 17. In cases of FTD without tau gene mutations, however, it is unclear whether genetic variability in the tau gene is associated with the development or modulation of FTD. OBJECTIVE: To determine whether genetic variability in tau and apolipoprotein E (ApoE) modulates and contributes to the development of FTD. Design and Patients The distribution of tau gene haplotypes and the ApoE genotype were investigated in 86 patients with well-characterized FTD and 50 control subjects. RESULTS: No difference in the distribution of the tau H1 and H2 haplotypes between FTD cases and controls was observed, whereas the ApoE epsilon4 allele was more frequent in FTD cases. The presence of at least 1 tau H2 allele was found to be significantly associated with an earlier age of onset in patients with FTD. The association between the H2 allele and age at onset was not related to family history, clinical presentation, or ApoE genotype. CONCLUSION: These findings support a role of tau protein in modulating disease phenotype by influencing the age at onset in these FTD cases.
BACKGROUND: The frontotemporal dementia (FTD) syndromes have been associated with the microtubule-associated tau protein since tau gene mutations have been demonstrated to be the cause of FTD and parkinsonism linked to chromosome 17. In cases of FTD without tau gene mutations, however, it is unclear whether genetic variability in the tau gene is associated with the development or modulation of FTD. OBJECTIVE: To determine whether genetic variability in tau and apolipoprotein E (ApoE) modulates and contributes to the development of FTD. Design and Patients The distribution of tau gene haplotypes and the ApoE genotype were investigated in 86 patients with well-characterized FTD and 50 control subjects. RESULTS: No difference in the distribution of the tau H1 and H2 haplotypes between FTD cases and controls was observed, whereas the ApoE epsilon4 allele was more frequent in FTD cases. The presence of at least 1 tau H2 allele was found to be significantly associated with an earlier age of onset in patients with FTD. The association between the H2 allele and age at onset was not related to family history, clinical presentation, or ApoE genotype. CONCLUSION: These findings support a role of tau protein in modulating disease phenotype by influencing the age at onset in these FTD cases.
Authors: David J Irwin; Corey T McMillan; EunRan Suh; John Powers; Katya Rascovsky; Elisabeth M Wood; Jon B Toledo; Steven E Arnold; Virginia M-Y Lee; Vivianna M Van Deerlin; John Q Trojanowski; Murray Grossman Journal: Neurology Date: 2014-07-03 Impact factor: 9.910
Authors: I Taes; A Goris; R Lemmens; M A van Es; L H van den Berg; A Chio; B J Traynor; A Birve; P Andersen; A Slowik; B Tomik; R H Brown; C E Shaw; A Al-Chalabi; S Boonen; L Van Den Bosch; B Dubois; P Van Damme; W Robberecht Journal: Neurology Date: 2010-05-25 Impact factor: 9.910
Authors: Anne Sieben; Tim Van Langenhove; Sebastiaan Engelborghs; Jean-Jacques Martin; Paul Boon; Patrick Cras; Peter-Paul De Deyn; Patrick Santens; Christine Van Broeckhoven; Marc Cruts Journal: Acta Neuropathol Date: 2012-08-14 Impact factor: 17.088
Authors: Anna-Lotta Kaivorinne; Johanna Krüger; Katja Kuivaniemi; Hannu Tuominen; Virpi Moilanen; Kari Majamaa; Anne M Remes Journal: BMC Neurol Date: 2008-12-17 Impact factor: 2.474