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

Neurology
Catherine LabbéOwen A Ross

Abstract

To assess the importance of MAPT variant p.A152T in the risk of synucleinopathies. 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. 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. 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. G...Continue Reading

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Citations

Mar 24, 2017·Brain : a Journal of Neurology·Ana LopezDavid C Rubinsztein
Dec 13, 2016·Cold Spring Harbor Perspectives in Biology·Flora I Hinz, Daniel H Geschwind
Apr 24, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Sudhanshu P RaikwarAsgar Zaheer
Jan 4, 2020·International Journal of Geriatric Psychiatry·Hazel SanghviAnto P Rajkumar
Jun 12, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Catherine LabbéOwen A Ross
Jan 23, 2019·Molecular Neurodegeneration·Tiago Fleming OuteiroIan McKeith
Jan 25, 2019·Acta Neuropathologica Communications·Yari CarlomagnoCasey Cook
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Aug 12, 2018·Current Neurology and Neuroscience Reports·Tatiana OrmeJose Bras
Aug 21, 2021·Scientific Reports·N CallizotP Verwaerde

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