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

J 2015

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

LABBÉ, Catherine, Kotaro OGAKI, Oswaldo LORENZO-BETANCOR, Alexandra I. SOTO-ORTOLAZA, Ronald L. WALTON et. al.

Basic information

Original name

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

Authors

LABBÉ, Catherine (840 United States of America), Kotaro OGAKI (840 United States of America), Oswaldo LORENZO-BETANCOR (840 United States of America), Alexandra I. SOTO-ORTOLAZA (840 United States of America), Ronald L. WALTON (840 United States of America), Sruti RAYAPROLU (840 United States of America), Shinsuke FUJIOKA (840 United States of America), Melissa E. MURRAY (840 United States of America), Michael G. HECKMAN (840 United States of America), Andreas PUSCHMANN (752 Sweden), Allan MCCARTHY (372 Ireland), Timothy LYNCH (372 Ireland), Joanna SIUDA (616 Poland), Grzegorz OPALA (616 Poland), Monika RUDZINSKA (616 Poland), Anna KRYGOWSKA-WAJS (616 Poland), Maria BARCIKOWSKA (616 Poland), Krzysztof CZYZEWSKI (616 Poland), Yanosh SANOTSKY (804 Ukraine), Irena REKTOROVÁ (203 Czech Republic, guarantor, belonging to the institution), Pamela J. MCLEAN (840 United States of America), Rosa RADEMAKERS (840 United States of America), Niluefer ERTEKIN-TANER (840 United States of America), Anhar HASSAN (840 United States of America), J. Eric AHLSKOG (840 United States of America), Bradley F. BOEVE (840 United States of America), Ronald C. PETERSEN (840 United States of America), Demetrius M. MARAGANORE (840 United States of America), Charles H. ADLER (840 United States of America), Tanis J. FERMAN (840 United States of America), Joseph E. PARISI (840 United States of America), Neill R. GRAFF-RADFORD (840 United States of America), Ryan J. UITTI (840 United States of America), Zbigniew K. WSZOLEK (840 United States of America), Dennis W. DICKSON (840 United States of America) and Owen A. ROSS (840 United States of America)

Edition

Neurology, Philadelphia, LIPPINCOTT WILLIAMS & WILKINS, 2015, 0028-3878

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.166

RIV identification code

RIV/00216224:14740/15:00085057

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1212/WNL.0000000000001946

UT WoS

000364338500009

Keywords in English

adult; aged; alpha synucleinopathies; Article; case control study; controlled study; degenerative disease; diffuse Lewy body disease; disease predisposition

Abstract

V originále

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.

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Citovat

LABBÉ, Catherine, Kotaro OGAKI, Oswaldo LORENZO-BETANCOR, Alexandra I. SOTO-ORTOLAZA, Ronald L. WALTON, Sruti RAYAPROLU, Shinsuke FUJIOKA, Melissa E. MURRAY, Michael G. HECKMAN, Andreas PUSCHMANN, Allan MCCARTHY, Timothy LYNCH, Joanna SIUDA, Grzegorz OPALA, Monika RUDZINSKA, Anna KRYGOWSKA-WAJS, Maria BARCIKOWSKA, Krzysztof CZYZEWSKI, Yanosh SANOTSKY, Irena REKTOROVÁ, Pamela J. MCLEAN, Rosa RADEMAKERS, Niluefer ERTEKIN-TANER, Anhar HASSAN, J. Eric AHLSKOG, Bradley F. BOEVE, Ronald C. PETERSEN, Demetrius M. MARAGANORE, Charles H. ADLER, Tanis J. FERMAN, Joseph E. PARISI, Neill R. GRAFF-RADFORD, Ryan J. UITTI, Zbigniew K. WSZOLEK, Dennis W. DICKSON and Owen A. ROSS. Role for the microtubule-associated protein tau variant p.A152T in risk of alpha-synucleinopathies. Neurology. Philadelphia: LIPPINCOTT WILLIAMS & WILKINS, 2015, vol. 85, No 19, p. 1680-1686. ISSN 0028-3878. Available from: https://dx.doi.org/10.1212/WNL.0000000000001946.

@article{1319706,
   author = {Labbé, Catherine and Ogaki, Kotaro and LorenzoandBetancor, Oswaldo and SotoandOrtolaza, Alexandra I. and Walton, Ronald L. and Rayaprolu, Sruti and Fujioka, Shinsuke and Murray, Melissa E. and Heckman, Michael G. and Puschmann, Andreas and McCarthy, Allan and Lynch, Timothy and Siuda, Joanna and Opala, Grzegorz and Rudzinska, Monika and KrygowskaandWajs, Anna and Barcikowska, Maria and Czyzewski, Krzysztof and Sanotsky, Yanosh and Rektorová, Irena and McLean, Pamela J. and Rademakers, Rosa and ErtekinandTaner, Niluefer and Hassan, Anhar and Ahlskog, J. Eric and Boeve, Bradley F. and Petersen, Ronald C. and Maraganore, Demetrius M. and Adler, Charles H. and Ferman, Tanis J. and Parisi, Joseph E. and GraffandRadford, Neill R. and Uitti, Ryan J. and Wszolek, Zbigniew K. and Dickson, Dennis W. and Ross, Owen A.},
   article_location = {Philadelphia},
   article_number = {19},
   doi = {http://dx.doi.org/10.1212/WNL.0000000000001946},
   keywords = {adult; aged; alpha synucleinopathies; Article; case control study; controlled study; degenerative disease; diffuse Lewy body disease; disease predisposition},
   language = {eng},
   issn = {0028-3878},
   journal = {Neurology},
   title = {Role for the microtubule-associated protein tau variant p.A152T in risk of alpha-synucleinopathies},
   url = {http://www.neurology.org/content/85/19/1728.2.short},
   volume = {85},
   year = {2015}
}

TY  - JOUR
ID  - 1319706
AU  - 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.
PY  - 2015
TI  - Role for the microtubule-associated protein tau variant p.A152T in risk of alpha-synucleinopathies
JF  - Neurology
VL  - 85
IS  - 19
SP  - 1680-1686
EP  - 1680-1686
PB  - LIPPINCOTT WILLIAMS & WILKINS
SN  - 00283878
KW  - adult
KW  - aged
KW  - alpha synucleinopathies
KW  - Article
KW  - case control study
KW  - controlled study
KW  - degenerative disease
KW  - diffuse Lewy body disease
KW  - disease predisposition
UR  - http://www.neurology.org/content/85/19/1728.2.short
L2  - http://www.neurology.org/content/85/19/1728.2.short
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. © 2015 American Academy of Neurology.
ER  -

LABBÉ, Catherine, Kotaro OGAKI, Oswaldo LORENZO-BETANCOR, Alexandra I. SOTO-ORTOLAZA, Ronald L. WALTON, Sruti RAYAPROLU, Shinsuke FUJIOKA, Melissa E. MURRAY, Michael G. HECKMAN, Andreas PUSCHMANN, Allan MCCARTHY, Timothy LYNCH, Joanna SIUDA, Grzegorz OPALA, Monika RUDZINSKA, Anna KRYGOWSKA-WAJS, Maria BARCIKOWSKA, Krzysztof CZYZEWSKI, Yanosh SANOTSKY, Irena REKTOROVÁ, Pamela J. MCLEAN, Rosa RADEMAKERS, Niluefer ERTEKIN-TANER, Anhar HASSAN, J. Eric AHLSKOG, Bradley F. BOEVE, Ronald C. PETERSEN, Demetrius M. MARAGANORE, Charles H. ADLER, Tanis J. FERMAN, Joseph E. PARISI, Neill R. GRAFF-RADFORD, Ryan J. UITTI, Zbigniew K. WSZOLEK, Dennis W. DICKSON and Owen A. ROSS. Role for the microtubule-associated protein tau variant p.A152T in risk of alpha-synucleinopathies. \textit{Neurology}. Philadelphia: LIPPINCOTT WILLIAMS \&{} WILKINS, 2015, vol.~85, No~19, p.~1680-1686. ISSN~0028-3878. Available from: https://dx.doi.org/10.1212/WNL.0000000000001946.

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