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Biomarkers of environmental exposure in Parkinson's disease discovered

 
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Last reviewed: 02.07.2025
 
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18 May 2024, 12:50

A team of researchers from Northwestern Medicine has discovered new DNA methylation patterns in the blood of patients with Parkinson's disease, according to results published in the journal Annals of Neurology.

The study, led by Paulina Gonzalez-Latapi, MD, MS, assistant professor in the Division of Movement Disorders in the Ken and Ruth Davey Department of Neurology, demonstrates the potential of using DNA methylation as a biomarker and diagnostic tool to identify disease risk in patients.

Parkinson's disease occurs when certain areas of the brain lose the ability to produce dopamine and ultimately regulate movement. The condition affects more than six million people worldwide, according to the Michael J. Fox Foundation for Parkinson's Research.

In addition to the known genetic causes of Parkinson's disease, recent studies also suggest that environmental factors may increase the risk of developing the disease. However, understanding the impact of environmental factors and genetic mutations on the risk of developing the disease remains poorly understood.

In the current study, the researchers examined DNA methylation profiles from blood samples from 196 patients with Parkinson's disease and 86 healthy participants enrolled in the Parkinson's Progression Markers Initiative (PPMI) study.

"DNA methylation, in a sense, serves as a memory of previous environmental exposures that ultimately alter the methylation signatures in our cells and bodies," Gonzalez-Latapi said.

The researchers first analyzed genome-wide methylation data to identify methylation changes in the participants’ whole blood samples (composed of red blood cells, white blood cells, and platelets) over the three-year study period. They then integrated this data with gene expression data obtained through RNA sequencing. Using a variety of approaches, the team found 75 differentially expressed genes with distinct methylation patterns in Parkinson’s patients compared with healthy controls.

Pathway enrichment for differentially methylated regions (DMRs) at baseline. Circle size represents the number of genes belonging to each pathway (larger circle = more genes). Source: Annals of Neurology (2024). DOI: 10.1002/ana.26923

Specifically, consistent differences in DNA methylation were noted in the CYP2E1 gene from baseline and throughout the three-year study period. The CYP2E1 protein is known to metabolize substrates, including pesticides, exposure to which has previously been linked to the development of Parkinson's disease, according to Gonzalez-Latapy.

"This is a significant step toward unraveling the complex interactions that occur in Parkinson's disease and may pave the way for identifying potential biomarkers for early diagnosis and progression," Gonzalez-Latapy said.

"Characterizing DNA methylation and gene expression patterns in the blood has the potential to help us understand the complex interactions between environmental and genetic factors in the development of Parkinson's disease," said Dimitri Crane, MD, Ph.D., the Aaron Montgomery Ward Professor and the Ken and Ruth Davey Chair in the Department of Neurology, senior author of the study.

"From a broader perspective, such patient-based studies will help classify patients with Parkinson's disease through a biological lens, which will ultimately facilitate the development of more precise treatments for patients with different subtypes of the disease."

Going forward, González-Latapy said, her team plans to study DNA methylation data in patients in the prodromal phase of Parkinson’s disease — those who are at risk for developing the disease but are not yet showing symptoms. They also hope to study how environmental exposures, such as pesticide exposure, influence methylation changes in patients over time, she added.

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