Direct genetic evidence for involvement of tau in progressive supranuclear palsy. European Study Group on Atypical Parkinsonism Consortium.
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.
Bennett
P
P
University Department of Clinical Neurology, Queen Elizabeth Hospital, Birmingham, UK.
Bonifati
V
V
Bonuccelli
U
U
Colosimo
C
C
De Mari
M
M
Fabbrini
G
G
Marconi
R
R
Meco
G
G
Nicholl
D J
DJ
Stocchi
F
F
Vanacore
N
N
Vieregge
P
P
Williams
A C
AC
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004252:DNA Mutational Analysis / Q000379:methods; D003937:Diagnosis, Differential; D018900:Dinucleotide Repeats; D005260:Female; D005456:Fluorescent Dyes; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis* / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis* / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
D005456:Fluorescent Dyes; D005819:Genetic Markers; D016875:tau Proteins