Before The Tremor: Parkinson's Can Be Detected in The Blood

Scientists have discovered that early signs of Parkinson's disease may be hidden in the blood, years before motor symptoms appear. Alterations in genes linked to DNA repair and cellular stress help identify people in the early stages of the disease, when the brain can still be protected. This discovery opens new possibilities for early diagnosis and preventive treatments.

Parkinson's disease is usually recognized when motor symptoms appear, such as tremors, slowness of movement, and muscle rigidity. However, when these signs appear, the brain has already suffered a significant loss of important neurons.

What many people don't know is that, years before this, the disease often gives silent signs, such as sleep problems, loss of smell, constipation, anxiety, and depression. This initial phase is called the prodromal phase and represents a valuable opportunity to identify the disease earlier.

Detecting Parkinson's before the onset of motor symptoms is crucial because, at this early stage, there are still many living neurons that can be protected. To this end, scientists are seeking to understand what biological changes occur in the body before the brain is severely affected.

One of the processes that has attracted much attention is the damage to the genetic material of cells, DNA, and the problems in the systems responsible for repairing this damage. The neurons most affected in Parkinson's disease produce dopamine and work intensely, which generates a large amount of highly reactive substances that can damage DNA.

Furthermore, in Parkinson's disease, mitochondria, structures responsible for producing energy, malfunction, further increasing this cellular stress. Over time, this damage accumulates and can exceed the cells' natural capacity to repair DNA, leading to neuronal death.

The body has defense mechanisms to repair DNA damage, one of the main ones being a system that identifies and removes damaged parts. This system is especially important within mitochondria, which have little repair capacity.

However, recent studies have shown that this process, when exaggerated or dysregulated, can become harmful. In experimental models, reducing the activity of certain genes involved in this repair ended up protecting neurons, showing that balance is essential.

A major challenge in studying these processes in humans is that it is not possible to directly access the brains of living people. Therefore, scientists began investigating whether signs of these alterations could be detected in the blood. The idea is that changes in genes related to DNA repair and cellular stress, visible in blood tests, may reflect what is happening in the brain, acting as an early sign of the disease.

In this study, researchers analyzed blood samples collected over time from three groups: healthy individuals, individuals in the prodromal phase of Parkinson's disease, and patients with established disease. They assessed which genes were more or less active, especially those linked to DNA repair and the cellular stress response.

To handle the enormous amount of data, machine learning techniques were used, which help identify complex patterns that are not visible to the naked eye.

The results showed that alterations in these genes can differentiate people in the prodromal phase from healthy individuals, especially in the more advanced stages of this initial phase.

Interestingly, these differences disappear when the disease is already established, suggesting that these mechanisms act mainly at the beginning of the process. This indicates that signals in the blood can serve as early biomarkers of Parkinson's disease, paving the way for early diagnoses and interventions before significant neuronal loss occurs.

READ MORE:

Longitudinal assessment of DNA repair signature trajectory in prodromal versus established Parkinson’s disease

Danish Anwer, Nicola Pietro Montaldo, Elva Maria Novoa-del-Toro, Diana Domanska, Hilde Loge Nilsen, and Annikka Polster

npj Parkinson’s Disease. 11, Article number: 349 (2025). 5 December 2025

DOI: 10.1038/s41531-025-01194-7

Abstract:

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. DNA repair dysfunction and integrated stress response (ISR) dysregulation have been implicated in PD pathophysiology, however, their role during the prodromal phase remains unclear. We analyzed longitudinal blood transcriptomic data from the Parkinson’s Progression Markers Initiative to assess DNA repair and ISR genes in healthy individuals, prodromal PD, and those with established PD. Logistic regression classifiers showed that DNA repair and ISR expression distinguished prodromal PD from healthy individuals, with accuracy peaking in later prodromal stages. In contrast, these pathways did not separate established PD from controls, suggesting a more prominent role early in progression. Gene expression variability in prodromal PD was high at baseline but decreased over time, indicating convergence as disease advances. Notably, 50% of DNA repair genes and 74% of ISR genes showed non-linear patterns, suggesting a transient adaptive response fading with progression. Feature importance analysis highlighted several predictors of prodromal PD, including ERCC6, PRIMPOL, NEIL2, and NTHL1. These findings indicate that DNA repair and ISR dysregulation are relevant in prodromal PD and may be biomarkers for early detection and intervention. Future research should validate these results in larger cohorts and evaluate diagnostic and therapeutic potential.