Polymorphisms in the tau gene in sporadic frontotemporal dementia and other neurodegenerative disorders

Abstract

The tau gene on chromosome 17 is fundamental in the pathogenesis of a number of neurodegenerative disorders. Mutations in tau are found in familial frontotemporal dementia (FTD) and the A0/A0 genotype associated with progressive supranuclear palsy (PSP). This study investigates the hypothesis that polymorphisms in the tau gene are associated with sporadic FTD. Western Australian populations of patients with sporadic frontotemporal dementia, PSP, Alzheimer's disease (AD), Huntington's disease (HD) and normal controls were studied. A new method was developed using fluorescently labelled probes to determine polymorphisms in the GT repeat region of intron 9. The A0/A0 genotype was found in 95% of PSP patients (n=20), 58.3% of FTD patients (n=48), 60.8% of AD patients (n=52), 75% of HD patients (n=40), and 75% of normal controls (n=40). None of these differences in genotype frequency were found to be significant by the Fisher exact test (P > 0.05). There were no significant differences in the frequencies of A0/A3 and A0/A1 haplotypes. We have not observed a significant increase in the A0/A0 genotype frequency in sporadic frontotemporal dementia suggesting that this polymorphism is unlikely to be related to the development of this condition. Furthermore, we have observed an increase in the A0/A0 genotype in PSP which did not reach statistical significance, suggesting that there may be population differences in the role of genetic factors in conferring risks to neurodegenerative disorders. Our work does not exclude that tau may interact with other genetic factors.

Course and Causes of Suspected Dementia in Young Adults: A Longitudinal Study

“…No mutations in the τ gene were observed in the FTLD group. 20 Within the FTLD group, 36 patients had the frontal variant of FTLD, 6 had primary progressive aphasia, and 1 was diagnosed with semantic dementia. A substantial number of patients with the suspicion of dementia were found to be normal.…”

Aging dependent effect of nuclear tau

“…For decades, tau has been considered a cytoplasmic tubulin binding neuro-protein, which plays an important role in the regulation of the microtubular network and in axonal formation (Povlishock et al, 1999). It has been found to be directly involved in the etiology of neurodegenerative disorders related to age, such as AD and other taupathies (Panegyres and Zafiris-Toufexis, 2002). However, more recently, the presence of tau has been demonstrated in non-neuronal cells, such as fibroblasts and lymphocytes, as well as in normal and transformed cell lines from different tissues (Cross et al, 2000;Souter and Lee 2009).…”

Tauopathies: One Disease or Many?

“…The exact mechanism by which the H1 haplotype confers an increased risk for these conditions is not known 111 . One study also reports an association between the A0 allele and FTLD 120 , whereas others do not support such an association 119,121 .…”