The Tau A0 Allele in Parkinson's Disease

Parkinson's disease (PD) is primarily an alpha-synucleinopathy, rather than a tauopathy, but there is evidence for an indirect association of tau with the pathogenetic process in PD. We therefore assessed the frequency in PD of the tau A0 allele, a dinucleotide repeat marker that has been associated with a sporadic tauopathy, progressive supranuclear palsy (PSP). We found the A0 allele to comprise 79.2% of 758 alleles from PD patients and 71.2% of 264 control alleles (P = 0.008). We also performed a meta-analysis of three previous reports, two of which failed to produce statistically significant results. Taken together, they also support a PD/A0 allelic association, even after correction for misdiagnosis of PSP as PD (P< 0.001). The A0/A0 genotype frequency in our patients (62.3%) did not differ significantly from that in controls (53.0%, P = 0.062), but the meta-analysis, even after correction for misdiagnosis, showed a significant result, with P = 0.002. The frequency of A0 allele and the A0/A0 genotype were compatible with Hardy-Weinberg equilibrium. The frequency of the A0 allele and the A0/A0 genotype in our patients with familial PD was not significantly greater than in those with sporadic PD. We conclude that the tau protein may play a small role in the pathogenesis of PD and that biochemical characterization of this role may suggest opportunities for PD prophylaxis.