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
References
Mar 1, 1992·Journal of Neurology, Neurosurgery, and Psychiatry·A J HughesA J Lees
Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Nov 1, 1996·Neurology·I G McKeithR H Perry
Jun 26, 1998·Nature·M HuttonP Heutink
Jun 19, 2002·Acta Neuropathologica·John E DudaJohn Q Trojanowski
Apr 26, 2003·Science·Benoit I GiassonVirginia M-Y Lee
Aug 7, 2004·American Journal of Human Genetics·Lisa SkipperMatthew Farrer
Oct 21, 2005·Neurology·I G McKeithUNKNOWN Consortium on DLB
Sep 22, 2006·Human Molecular Genetics·Alan M PittmanRohan de Silva
Mar 18, 2008·Neuroscience·G MuntanéI Ferrer
Aug 30, 2008·Neurology·S GilmanM Vidailhet
Dec 24, 2010·Clinical Neuropathology·G G KovacsH Budka
Feb 16, 2011·Neurology·C Vilariño-GüellO A Ross
Mar 23, 2012·PLoS Genetics·Christina M LillLars Bertram
May 5, 2012·Human Molecular Genetics·Giovanni CoppolaDaniel H Geschwind
May 19, 2012·Neurobiology of Aging·Eleanna KaraTamas Revesz
Jul 13, 2012·Neurology·Manu SharmaUNKNOWN GEO-PD Consortium
Apr 23, 2013·Parkinsonism & Related Disorders·Catherine LabbéOwen A Ross
Nov 23, 2013·Parkinsonism & Related Disorders·Heather McCannGlenda M Halliday
Jun 29, 2014·Human Molecular Genetics·Jose BrasJohn Hardy
Jul 30, 2014·Nature Genetics·Mike A NallsAndrew B Singleton
Oct 30, 2014·Molecular Neurodegeneration·Simon MoussaudPamela J McLean
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
Mar 5, 2016·EMBO Reports·Sumihiro MaedaLennart Mucke
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
Oct 17, 2018·Journal of Neurology·Eun-Joo KimLea T Grinberg
Jan 23, 2019·Molecular Neurodegeneration·Tiago Fleming OuteiroIan McKeith
Jan 25, 2019·Acta Neuropathologica Communications·Yari CarlomagnoCasey Cook
Apr 13, 2017·Acta Neuropathologica·Tara L Spires-JonesDietmar Rudolf Thal
May 15, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Jiao LiZiv Gan-Or
Dec 28, 2018·Human Molecular Genetics·Victoria J ButlerAimee W Kao
Jul 5, 2018·Molecular Diagnosis & Therapy·Jill S Goldman, Vivianna M Van Deerlin
Aug 12, 2018·Current Neurology and Neuroscience Reports·Tatiana OrmeJose Bras
May 1, 2021·International Journal of Molecular Sciences·Romina CombiLuigi Ferini-Strambi
Aug 21, 2021·Scientific Reports·N CallizotP Verwaerde
Aug 25, 2021·Scientific Reports·Chialin ChengStephen J Haggarty