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NEUROLOGY 1998;51:982-985
© 1998 American Academy of Neurology

Direct genetic evidence for involvement of tau in progressive supranuclear palsy

P. Bennett, PhD, V. Bonifati, MD, U. Bonuccelli, MD, C. Colosimo, MD, M. De Mari, MD, G. Fabbrini, MD, R. Marconi, MD, G. Meco, MD, D. J. Nicholl, MRCP, F. Stocchi, MD, N. Vanacore, MD, P. Vieregge, MD, A. C. Williams, MD and European Study Group on Atypical Parkinsonism Consortium*

From the University Department of Clinical Neurology (Drs. Bennett, Nicholl, and Williams), Queen Elizabeth Hospital, Birmingham, UK; the Department of Neurosciences (Drs. Bonifati, Colosimo, Fabbrini, Meco, Stocchi, and Vanacore), "La Sapienza" University, Rome, Italy; the Institute of Neurology (Dr. Bonuccelli), University of Pisa, Italy; the Institute of Neurology (Dr. De Mari), University of Bari, Italy; the Neurology Section (Dr. Marconi), "Misericordia" Hospital, Grosseto, Italy; and the Department of Neurology (Dr. Vieregge), Medical University of Lubeck, Germany.

Address correspondence and reprint requests to Dr. Phil Bennett, University of Birmingham, Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2QZ UK.

Objective: To confirm whether a dinucleotide repeat sequence in an intron of the microtubule-associated protein tau is associated with progressive supranuclear palsy (PSP) in an independent study population and to establish an improved methodology for allelotyping.

Background: It has recently been reported that a genetic variant of tau, known as the A0 allele, was represented excessively in PSP patients when compared with control subjects.

Methods: In a multicenter study, the authors examined the allelic distribution of this dinucleotide repeat marker in a set of clinically ascertained PSP patients (n = 30), multiple system atrophy (MSA) patients (n = 35), and matched control subjects (n = 70). Individuals were allelotyped using automated analysis of fluorescently labeled PCR products.

Results: The A0 allele was significantly overrepresented in the PSP patients (93.3% versus 76.4%; p = 0.0067; odds ratio [OR] = 4.33; 95% confidence interval [CI], 1.36 to 13.60), but not in the MSA patients. Likewise, A0 homozygotes were overrepresented in the PSP group (86.7% versus 61.1%; p = 0.02; OR = 4.14; 95% CI, 1.19 to 14.48) compared with control subjects.

Conclusions: The findings of this study, which is the largest to date, support those of a previous investigation that used pathologically confirmed PSP patients. These data provide additional strong evidence that genetic variation at or near the tau gene plays an important role in the pathogenesis of PSP.

*See the Appendix on page 985 for a listing of additional members of the ESGAP Consortium.

Supported by the Italian Ministry for University, Scientific and Technological Research grants to G.M.

Received February 18, 1998. Accepted in final form June 27, 1998.






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