Parkinson's disease and REM sleep behavior disorder

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 1-2% of the population older than 60 years. As the world's population is aging, the burden of PD is expected to dramatically increase in the next decades. PD is a progressive disease, characterized by a variety of motor and non-motor symptoms, which typically manifest after the age of 60, but can occur at a much earlier stage. One of those non motor symptoms, is REM sleep behavior disorder (RBD). Individuals with RBD, during REM sleep, lose their muscle inhibition, and enact their dreams. In average, about 10 years after the onset of RBD, these individuals may develop PD or another synucleinopathy (see page on RBD and other synucleinopathies).

Conversion from RBD to synucleinopathies.

Taken from Postuma RB et al., Neurology, 2015

In our RBD genetics project, we collaborate with numerous centers from around the world, and have collected the world's largest genetic cohort of patients with RBD. These patients are being followed up by our collaborators, and their conversion to overt synucleinopathies is documented. In our project on RBD and PD, we examine how genetics affect the risk for RBD and progression to PD. This project includes various sub-projects, for example:

  • Genome wide association study to identify risk loci for RBD

  • Machine learning approach to use genetics and clinical variable to predict conversion from RBD to overt synucleinopathies

  • Mendelian randomization studies to identify modifiable risk factors and druggable targets

  • Lysosomal genes in RBD

  • Targeted next generation sequencing of multiple PD genes in RBD

  • Polygenic risk score and heritability of RBD

  • Digenic inheritance in RBD and PD

  • Copy number variations in RBD and PD

  • Whole genome sequencing of RBD

  • Genetic stratification of RBD patients towards future clinical trials

  • Generating iPSCs from RBD and PD patients with genetic variants in PD-related genes

Selected publications on RBD and PD

  • RBD genetics only partially overlaps PD genetics - PubMed

  • GBA mutations are important in RBD - PubMed

  • APOE e4 allele does not affect risk for RBD - PubMed

  • PINK1 heterozygous variants may be associated with RBD - PubMed

  • LRRK2 protective haplotype in RBD -  PubMed

  • MAPT haplotypes in RBD and PD - PubMed

  • TMEM175 is associated with RBD and with GBA activity - PubMed

  • Fine mapping of the SNCA region reveals distinct associations with RBD and PD - PubMed

    1033 Pine Avenue West

    Ludmer Pavilion, room 312

    Montreal, QC, H3A 1A1

    Lab: +1-514-398-5845

    e-mail: ziv.gan-or@mcgill.ca