TY - JOUR
T1 - Role for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies
AU - Labbé, Catherine
AU - Ogaki, Kotaro
AU - Lorenzo-Betancor, Oswaldo
AU - Soto-Ortolaza, Alexandra I.
AU - Walton, Ronald L.
AU - Rayaprolu, Sruti
AU - Fujioka, Shinsuke
AU - Murray, Melissa E.
AU - Heckman, Michael G.
AU - Puschmann, Andreas
AU - McCarthy, Allan
AU - Lynch, Timothy
AU - Siuda, Joanna
AU - Opala, Grzegorz
AU - Rudzinska, Monika
AU - Krygowska-Wajs, Anna
AU - Barcikowska, Maria
AU - Czyzewski, Krzysztof
AU - Sanotsky, Yanosh
AU - Rektorová, Irena
AU - McLean, Pamela J.
AU - Rademakers, Rosa
AU - Ertekin-Taner, Nilüfer
AU - Hassan, Anhar
AU - Ahlskog, J. Eric
AU - Boeve, Bradley F.
AU - Petersen, Ronald C.
AU - Maraganore, Demetrius M.
AU - Adler, Charles H.
AU - Ferman, Tanis J.
AU - Parisi, Joseph E.
AU - Graff-Radford, Neill R.
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew K.
AU - Dickson, Dennis W.
AU - Ross, Owen A.
N1 - Publisher Copyright:
© 2015 American Academy of Neurology.
PY - 2015/11/10
Y1 - 2015/11/10
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000001946
DO - 10.1212/WNL.0000000000001946
M3 - Article
C2 - 26333800
AN - SCOPUS:84946916693
SN - 0028-3878
VL - 85
SP - 1680
EP - 1686
JO - Neurology
JF - Neurology
IS - 19
ER -