A spatial transcriptomics study from scientists at the Van Andel Institute has shed light on the complex molecular changes that occur in brain cells with Lewy bodies, a key pathological hallmark of Parkinson's disease and certain dementias.
The findings, published in Nature Communications, reveal that brain cells with Lewy bodies exhibit a distinct gene expression pattern, akin to a disease-related fingerprint. This discovery offers a crucial starting point for better understanding how cells respond to Lewy bodies, a crucial area for developing new therapies.
"We've long known that Lewy bodies play a role in Parkinson's and other neurodegenerative diseases, but there are still many unanswered questions," said Michael Henderson, the study's corresponding author. "Why are some cells more susceptible to Lewy bodies than others? How do Lewy bodies actually affect cells? Our findings provide an important foundation for addressing these questions."
Lewy bodies are clumps of misshapen proteins that are believed to disrupt healthy cellular function and contribute to cell death in neurodegenerative disorders. The loss of these vital cells is a key factor in the development of disease symptoms.
Leveraging recent technological advancements, including spatial transcriptomics, the research team was able to compare brain cells with Lewy bodies to those without in unprecedented detail. The identified pattern includes genes that affect critical processes required for brain health, such as cellular communication, energy regulation, cellular waste removal, and inflammation.
"Our findings support the idea that cells with Lewy bodies affect other cells and processes in the brain," Henderson said. "Moving forward, we plan to explore the molecular pathways disrupted by Lewy bodies to identify mechanisms that may be protective."