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.
journal_name
Neurologyjournal_title
Neurologyauthors
Labbé C,Ogaki K,Lorenzo-Betancor O,Soto-Ortolaza AI,Walton RL,Rayaprolu S,Fujioka S,Murray ME,Heckman MG,Puschmann A,McCarthy A,Lynch T,Siuda J,Opala G,Rudzinska M,Krygowska-Wajs A,Barcikowska M,Czyzewski K,Sanotsky Ydoi
10.1212/WNL.0000000000001946subject
Has Abstractpub_date
2015-11-10 00:00:00pages
1680-6issue
19eissn
0028-3878issn
1526-632Xpii
WNL.0000000000001946journal_volume
85pub_type
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