SIGNIFICANT CHANGES IN THE TAU-A0 AND A3 ALLELES IN PROGRESSIVE SUPRANUCLEAR PALSY AND IMPROVED GENOTYPING BY SILVER DETECTION

Background: Progressive supranuclear palsy (PSP) is characterized by i ntraneuronal inclusions of neurofibrillary tangles formed by aggregate d tau protein. A significant association between the tau gene A0/A0 ge notype 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, an d to standardize a nonradioactive method for tau gene genotyping. Sett ing: Hospital and university research laboratories. Subjects and Metho ds: To facilitate genotyping of the tau gene, we standardized the cond itions for silver-based detection of the tau gene dinucleotide polymor phism. Thirty patients from Spain clinically diagnosed as having proba ble 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 geno type were found in the Spanish patients with PSP compared with the con trol group. A method based on silver detection was standardized for th e genotyping of the tau gene. Conclusions: The detection of a signific ant association between the tau gene A0/A0 genotype and PSP in 2 indep endent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 g enotype is a risk factor for developing PSP independent of genetic bac kground. Alternatively, the results could be interpreted as a protecti ve effect of the A3 allele.