Project Overview

When we dream, our bodies are normally paralyzed so we don’t act out the dream. In isolated REM sleep behavior disorder (iRBD), that safety switch fails: people may talk, shout, punch, or kick during sleep. iRBD is important because most people with it will later develop a brain disease like Parkinson’s disease or dementia with Lewy bodies. This gives us a rare “early warning” stage when help may make the biggest difference.

Our project asks a simple question with big implications: do signs of inflammation in the blood line up with early changes we can see on brain scans in people with iRBD? If they do, a routine blood test might inform on brain neurodegeneration and guide prevention trials.

We will study iRBD volunteers from the long-running Montreal iRBD cohort. First, we will analyze blood plasma for a high-throughput test that measures over a thousand proteins tied to immune and inflammatory pathways. We will profile immune cells at single-cell resolution and read their T-cell receptors to see which cell types and immune “programs” are active. At the same time, we will use MRI to measure three sensitive signs of early brain injury: extra water around brain cells (“free water”), shrinkage of vulnerable regions, and a fluid-clearance measure that reflects how well the brain removes waste. Using robust statistical tools, we will then look for patterns (which blood signals go with which brain changes?) and then test whether those patterns relate to clinical changes.

This work unites specialists in brain imaging, blood-based inflammation assays and immune cell profiling, and clinical leadership. In the short term, we aim to deliver clear blood-brain signatures of risk in iRBD. In the longer term, these findings could help identify who needs closer follow-up, select people for preventive trials, and point to novel targets for treatments.

Principal Investigator

Shady Rahayel , Université de Montréal

Team Members

Jo Anne Stratton, Montreal Neurological Institute, McGill University

Martine Tetreault, University of Montreal

Ronald Postuma, McGill University

Christina Tremblay, CIUSSS-du-Nord-de-l’Ile-de-Montreal

Veronique Daneault, CIUSSS-du-Nord-de-l’Ile-de-Montreal

Alexandre Pastor-Bernier, CIUSSS-du-Nord-de-l’Ile-de-Montreal

Partners and Donors

Krembil Foundation