Common variation at the LRRK2 locus is associated with survival in the primary tauopathy progressive supranuclear palsy
Jabbari, E.; Tan, M. M. X.; Reynolds, R. H.; Mok, K. Y.; Ferrari, R.; Murphy, D. P.; Valentino, R. R.; Ross, O. A.; Dickson, D. W.; Al-Sarraj, S.; Gentleman, S. M.; Allinson, K. S. J.; Jaunmuktane, Z.; Holton, J. L.; Revesz, T.; Warner, T. T.; Lees, A. J.; Cookson, M. R.; Gibbs, J. R.; Ding, J.; Chia, R.; Traynor, B. J.; Scholz, S. W.; Pantelyat, A.; Viollet, C.; Dalgard, C. L.; Pletnikova, O.; Troncoso, J. C.; Boxer, A. L.; Respondek, G.; Hoglinger, G. U.; Burn, D. J.; Pavese, N.; Gerhard, A.; Kobylecki, C.; Leigh, P. N.; Church, A.; Hu, M. T. M.; Rowe, J. B.; Ryten, M.; Hardy, J.; Shoai, M.;
Show abstract
The genetic basis of variation in the rate of disease progression of primary tauopathies has not been determined. In two independent progressive supranuclear palsy cohorts, we show that common variation at the LRRK2 locus determines survival from motor symptom onset to death, possibly through regulation of gene expression. This links together genetic risk in alpha-synuclein and tau disorders, and suggests that modulation of proteostasis and neuro-inflammation by LRRK2 inhibitors may have a therapeutic role across disorders.
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