1. Role for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies
- Author
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Oswaldo Lorenzo-Betancor, Andreas Puschmann, Yanosh Sanotsky, Melissa E. Murray, Shinsuke Fujioka, Ronald C. Petersen, Grzegorz Opala, Rosa Rademakers, J. Eric Ahlskog, Maria Barcikowska, Owen A. Ross, Kotaro Ogaki, Bradley F. Boeve, Monika Rudzińska, Alexandra I. Soto-Ortolaza, Allan McCarthy, Joseph E. Parisi, Krzysztof Czyzewski, Neill R. Graff-Radford, Sruti Rayaprolu, Niluefer Ertekin-Taner, Charles H. Adler, Tanis J. Ferman, Ronald L. Walton, Anhar Hassan, Pamela J. McLean, Irena Rektorová, Dennis W. Dickson, Joanna Siuda, Demetrius M. Maraganore, Zbigniew K. Wszolek, Catherine Labbé, Timothy Lynch, Michael G. Heckman, Anna Krygowska-Wajs, and Ryan J. Uitti
- Subjects
Male ,Pathology ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,030212 general & internal medicine ,Aged, 80 and over ,0303 health sciences ,biology ,Chemistry ,Parkinson Disease ,Middle Aged ,Penetrance ,3. Good health ,Cell biology ,alpha-Synuclein ,Female ,Psychology ,Adult ,Lewy Body Disease ,medicine.medical_specialty ,Adolescent ,Tau protein ,tau Proteins ,Article ,Young Adult ,03 medical and health sciences ,Atrophy ,Microtubule associated protein tau ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,030304 developmental biology ,Aged ,Alpha-synuclein ,Synucleinopathies ,Dementia with Lewy bodies ,Case-control study ,Genetic Variation ,Correction ,Odds ratio ,Multiple System Atrophy ,medicine.disease ,Minor allele frequency ,Case-Control Studies ,biology.protein ,Human medicine ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2015