Background: Progressive supranuclear palsy (PSP) is characterized by intraneuronal inclusions of neurofibrillary tangles formed by aggregated tau protein. A significant association between the tau gene A0/A0 genotype and PSP recently has been reported.
Objectives: To determine if a significant association between the tau gene A0/A0 genotype and PSP could be found in an independent population with a genetic background different from that in which the initial association was reported, and to standardize a nonradioactive method for tau gene genotyping.
Setting: Hospital and university research laboratories.
Subjects and methods: To facilitate genotyping of the tau gene, we standardized the conditions for silver-based detection of the tau gene dinucleotide polymorphism. Thirty patients from Spain clinically diagnosed as having probable PSP were included in the study and compared with different control groups.
Results: A highly significant overrepresentation of the A0/A0 genotype (P<.001) and a decrease in the frequency of the A0/A3 genotype were found in the Spanish patients with PSP compared with the control group. A method based on silver detection was standardized for the genotyping of the tau gene.
Conclusions: The detection of a significant association between the tau gene A0/A0 genotype and PSP in 2 independent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 genotype is a risk factor for developing PSP independent of genetic background. Alternatively, the results could be interpreted as a protective effect of the A3 allele.