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.
Golbe
L I
LI
Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA. golbe@umdnj.edu
Lazzarini
A M
AM
Spychala
J R
JR
Johnson
W G
WG
Stenroos
E S
ES
Mark
M H
MH
Sage
J I
JI
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000145:classification / Q000235:genetics*; D020033:Protein Isoforms; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D051843:Synucleins; D016875:tau Proteins / Q000235:genetics*
D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D051843:Synucleins; D016875:tau Proteins