Mapping Gene Signatures Unveils How Lewy Bodies Impact Brain Cells

A new study by scientists at Van Andel Institute provides an initial glimpse into the intricate molecular changes taking place in brain cells with Lewy bodies, crucial pathological markers of Parkinson’s disease and certain dementias.

The findings, published in the journal Nature Communications, unveil that brain cells harboring Lewy bodies display a distinct gene expression pattern resembling a disease-related fingerprint.

We’ve long known that Lewy bodies play a role in Parkinson’s and other neurodegenerative diseases but there are still many unanswered questions. Why are some cells more susceptible to Lewy bodies than others? How do Lewy bodies actually affect cells? Our findings are an important starting point for better understanding how cells respond to Lewy bodies, which is an area of great potential for informing new therapies.”

Michael Henderson Ph.D., Assistant Professor and Study Corresponding Author, Van Andel Institute

Clumps of distorted proteins known as Lewy bodies are thought to cause abnormal cellular activity and ultimately lead to cell death in neurodegenerative diseases like Parkinson's and Lewy body dementia. The loss of these essential cells exacerbates disease symptoms.

Recent technological developments, particularly the development of a novel method known as spatial transcriptomics, allowed Henderson and his colleagues to make a detailed comparison between brain cells with and without Lewy bodies.

The pattern they discovered involves genes impacting numerous vital functions necessary for brain health, such as inflammation, energy regulation, cellular waste removal, and cell communication. Preclinical models and Parkinson's disease patient cells were used in the investigation.

Our findings support the idea that cells with Lewy bodies affect other cells and processes in the brain. Moving forward, we plan to explore the molecular pathways disrupted by Lewy bodies to identify mechanisms that may be protective.”

Michael Henderson Ph.D., Assistant Professor and Study Corresponding Author, Van Andel Institute

Source:
Journal reference:

Goralski, M. T., et al. (2024) Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology. Nature Communications. doi.org/10.1038/s41467-024-47027-8

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