Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia

P. Poorkaj, M. Grossman, E. Steinbart, H. Payami, A. Sadovnick, D. Nochlin, T. Tabira, J. Q. Trojanowski, S. Borson, D. Galasko, S. Reich, B. Quinn, G. Schellenberg, T. D. Bird

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149 Scopus citations


Backgrounds: Mutations in the tau gene have been reported in families with frontotemporal dementia (FTD) linked to chromosome 17. It remains uncertain how commonly such mutations are found in patients with FTD or non-Alzheimer dementia with or without a positive family history. Objectives: To determine the frequency of tau mutations in patients with non-Alzheimer dementia. Patients and Methods: One hundred one patients with non-Alzheimer, nonvascular dementia, most thought to have FTD. Of these, 57 had a positive family history of dementia. Neuropathologic findings were available in 32. The tau gene was sequenced for all exons including flanking intronic DNA, portions of the 3′ and 5′ untranslated regions, and at least 146 base pairs in the intron following exon 10. Results: Overall, the frequency of the tau mutations was low, being 5.9% (6/101) in the entire group. No mutations were found in the 44 sporadic cases. However, 6 (10.5%) of the 57 familial cases and 4 (33%) of the 12 familial cases with tau pathologic findings had mutations in the tau gene. The most common mutation was P301L. Conclusions: We conclude that tau mutations are uncommon in a neurology referral population with non-Alzheimer dementia, even in those with a clinical diagnosis of FTD. However, a positive family history and/or tau pathologic findings increase the likelihood of a tau mutation. There must be other genetic and nongenetic causes of FTD and non-Alzheimer dementia, similar to the etiologic heterogeneity present in Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)383-387
Number of pages5
JournalArchives of Neurology
Issue number3
StatePublished - 2001


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