Informace o publikaci

Role for the microtubule-associated protein tau variant p.A152T in risk of alpha-synucleinopathies

Autoři	LABBÉ Catherine OGAKI Kotaro LORENZO-BETANCOR Oswaldo SOTO-ORTOLAZA Alexandra I. WALTON Ronald L. RAYAPROLU Sruti FUJIOKA Shinsuke MURRAY Melissa E. HECKMAN Michael G. PUSCHMANN Andreas MCCARTHY Allan LYNCH Timothy SIUDA Joanna OPALA Grzegorz RUDZINSKA Monika KRYGOWSKA-WAJS Anna BARCIKOWSKA Maria CZYZEWSKI Krzysztof SANOTSKY Yanosh REKTOROVÁ Irena MCLEAN Pamela J. RADEMAKERS Rosa ERTEKIN-TANER Niluefer HASSAN Anhar AHLSKOG J. Eric BOEVE Bradley F. PETERSEN Ronald C. MARAGANORE Demetrius M. ADLER Charles H. FERMAN Tanis J. PARISI Joseph E. GRAFF-RADFORD Neill R. UITTI Ryan J. WSZOLEK Zbigniew K. DICKSON Dennis W. ROSS Owen A.
Rok publikování	2015
Druh	Článek v odborném periodiku
Časopis / Zdroj	Neurology
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.neurology.org/content/85/19/1728.2.short
Doi	http://dx.doi.org/10.1212/WNL.0000000000001946
Obor	Neurologie, neurochirurgie, neurovědy
Klíčová slova	adult; aged; alpha synucleinopathies; Article; case control study; controlled study; degenerative disease; diffuse Lewy body disease; disease predisposition
Přiložené soubory	ZVV_2015_143_1319706_Role_of_the_microtubule.pdf
Popis	Objective: To assess the importance of MAPT variant p.A152T in the risk of synucleinopathies. Methods: In this case-control study, we screened a large global series of patients and controls, and assessed associations between p.A152T and disease risk. We included 3,229 patients with clinical Parkinson disease (PD), 442 with clinical dementia with Lewy bodies (DLB), 181 with multiple system atrophy (MSA), 832 with pathologically confirmed Lewy body disease (LBD), and 2,456 healthy controls. Results: The minor allele frequencies (MAF) in clinical PD cases (0.28%) and in controls (0.2%) were not found to be significantly different (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.63-2.98, p 0.42). However, a significant association was observed with clinical DLB (MAF 0.68%, OR 5.76, 95% CI 1.62-20.51, p 0.007) and LBD (MAF 0.42%, OR 3.55, 95% CI 1.04-12.17, p 0.04). Additionally, p.A152T was more common in patients with MSA compared to controls (MAF 0.55%, OR 4.68, 95% CI 0.85-25.72, p 0.08) but this was not statistically significant and therefore should be interpreted with caution. Conclusions: Overall, our findings suggest that MAPT p.A152T is a rare low penetrance variant likely associated with DLB that may be influenced by coexisting LBD and AD pathology. Given the rare nature of the variant, further studies with greater sample size are warranted and will help to fully explain the role of p.A152T in the pathogenesis of the synucleinopathies. © 2015 American Academy of Neurology.