Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world and affects over 100,000 Canadians. It causes movement difficulties and other symptoms that worsen over time. Although treatments can relieve symptoms, none can stop or slow the progression of the disease. Scientists have long focused on brain cells as the main source of damage in PD, but new evidence suggests that immune cells circulating in the blood may also play a crucial role. Our research explores how blood immune cells, called peripheral blood mononuclear cells (PBMCs), might harm brain cells in PD. Using a highly innovative “brain-on-a-chip” system that mimics the human blood-brain barrier (BBB)—the natural wall that separates the blood from the brain—we discovered that PBMCs from PD patients can damage neurons without actually crossing into the brain. This surprising finding challenges the traditional belief that immune cells must physically enter the brain to cause harm. We also found that specific brain support cells, called pericytes, appear to act as intermediaries, transmitting damaging signals from PBMCs to neurons. Our project will identify which immune cell types are responsible, how pericytes amplify their harmful effects, and whether similar processes occur in living organisms. This research could transform how scientists understand and treat PD. By revealing how the immune system communicates with the brain, even without breaching the BBB, we may uncover new therapeutic targets that can be reached through the bloodstream—bypassing one of the biggest challenges in brain medicine. In the long term, this work may lead to more effective and personalized treatments for people living with PD, offering new hope to patients and families affected by this devastating condition.
