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Frequency of Tau Gene Mutations in Familial and Sporadic Cases of Non-Alzheimer Dementia
Parvoneh Poorkaj, PhD;
Murray Grossman, MD;
Ellen Steinbart, MA;
Haydeh Payami, PhD;
Adele Sadovnick, PhD;
David Nochlin, MD;
Takeshi Tabira, MD;
John Q. Trojanowski, MD, PhD;
Soo Borson, MD;
Douglas Galasko, MD;
Stephen Reich, MD;
Bruce Quinn, MD, PhD;
Gerard Schellenberg, PhD;
Thomas D. Bird, MD
Arch Neurol. 2001;58:383-387.
Background 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.
Objective 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.
From the Departments of Medicine (Drs Poorkaj, Schellenberg, and Bird
and Ms Steinbart), Neurology (Drs Schellenberg and Bird), Pathology (Dr Nochlin),
and Psychiatry (Drs Borson, Schellenberg, and Bird), University of Washington,
Seattle; Geriatrics Research Education Clinical Center, Puget Sound Veterans
Affairs Health Care System, Seattle (Drs Poorkaj, Schellenberg, and Bird and
Ms Steinbart); Departments of Neurology and Pathology, University of Pennsylvania,
Philadelphia (Drs Grossman and Trojanowski); Department of Genetics, Oregon
Health Sciences University, Portland (Dr Payami); Department of Medical Genetics,
University of British Columbia, Vancouver (Dr Sadovnick); National Institute
of Neuroscience, Tokyo, Japan (Dr Tabira); Department of Neurology, University
of California, San Diego (Dr Galasko); Department of Neurology, The Johns
Hopkins University School of Medicine, Baltimore, Md (Dr Reich); and Department
of Cognitive Neurology and AD Center, Northwestern University, Chicago, Ill
(Dr Quinn).
Corresponding author and reprints: Thomas D. Bird, MD, Geriatrics
Research Education Clinical Center 182 B, VA Medical Center, 1660 S Columbian
Way, Seattle, WA 98108 (e-mail: tomnroz{at}u.washington.edu).
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