MAPT association with REM sleep behavior disorder

Idiopathic REM sleep behavior disorder (IRBD) is a REM sleep parasomnia comprising unpleasant dreams, dream-enacting behaviors, and loss of muscle atonia during REM sleep. Longitudinal studies have demonstrated that because most patients with IRBD develop with time Parkinson disease (PD) and other synucleinopathies including dementia with Lewy bodies (DLB) or multiple system atrophy (MSA), IRBD represents a prodromal stage of these diseases. In PD, 5%–10% of cases are caused by nonfrequent mendelian mutations segregating with disease in pedigrees, but the vast majority of cases are sporadic. Unbiased genome-wide association studies in sporadic PD (sPD) have shown that single nucleotide polymorphisms (SNPs) in the a-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes modulate disease susceptibility. Given that IRBD often antedates sPD and that, akin to PD, familial clustering of IRBD is rare, we hypothesized that genetically shared variation at SNCA and MAPT may influence disease susceptibility to both conditions. Accordingly, we genotyped PD-associated genetic variants in SNCA and MAPT in a cohort of Spanish patients with IRBD.