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

Labbé, Catherine ; Ogaki, Kotaro ; Lorenzo-Betancor, Oswaldo ; Soto-Ortolaza, Alexandra I ; Walton, Ronald L ; Rayaprolu, Sruti ; Fujioka, Shinsuke ; Murray, Melissa E ; Heckman, Michael G and Puschmann, Andreas LU orcid , et al. (2015) In Neurology 85(19). p.1680-1686
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... (More)
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 (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
85
issue
19
pages
1680 - 1686
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000364338500009
  • pmid:26333800
  • scopus:84946916693
  • pmid:26333800
ISSN
1526-632X
DOI
10.1212/WNL.0000000000001946
language
English
LU publication?
yes
id
2ae5e760-94f2-4122-81c7-09766f81d24e (old id 8043350)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26333800?dopt=Abstract
date added to LUP
2016-04-01 13:45:50
date last changed
2025-04-04 15:23:29
@article{2ae5e760-94f2-4122-81c7-09766f81d24e,
  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}},
  author       = {{Labbé, Catherine and Ogaki, Kotaro and Lorenzo-Betancor, Oswaldo and Soto-Ortolaza, 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 Krygowska-Wajs, Anna and Barcikowska, Maria and Czyzewski, Krzysztof and Sanotsky, Yanosh and Rektorová, Irena and McLean, Pamela J and Rademakers, Rosa and Ertekin-Taner, Nilüfer 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 Graff-Radford, Neill R and Uitti, Ryan J and Wszolek, Zbigniew K and Dickson, Dennis W and Ross, Owen A}},
  issn         = {{1526-632X}},
  language     = {{eng}},
  number       = {{19}},
  pages        = {{1680--1686}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Neurology}},
  title        = {{Role for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies.}},
  url          = {{http://dx.doi.org/10.1212/WNL.0000000000001946}},
  doi          = {{10.1212/WNL.0000000000001946}},
  volume       = {{85}},
  year         = {{2015}},
}