Parkinson's disease makes it difficult for the brain to control the nerve signals that regulate movement. This leads to the typical motor problems such as tremors, impaired balance, slowness of movement (bradykinesia) and muscle stiffness.
"In Parkinson's, large numbers of nerve cells in the brain are gradually lost. By the time motor symptoms appear and the diagnosis is made, 50-80 per cent of the relevant nerve cells are often already damaged or gone," explains Hilde Loge Nilsen, a researcher at the Department of Microbiology at the University of Oslo (UiO) and Oslo University Hospital (OUS).
Around 13,000 people in Norway live with Parkinson's, and more than 10 million are affected worldwide. There is still no cure.
"That is why we are searching for early traces of the disease, before the symptoms become obvious. This gives us an opportunity to understand what happens as the disease develops and, in future, to start treatment before the brain is permanently damaged," Loge Nilsen says.
A Parkinson's "signature" in the blood
Until now, there has been no reliable screening method for detecting this chronic neurological disease at an early stage. Loge Nilsen and her colleagues have now identified a biological signature - a pattern in the blood - that can reveal the disease before the classic motor symptoms appear.
The signature suggests that there is a phase in which cells are actively fighting the disease. Because this can be measured in the blood, it can act as a biomarker for Parkinson's, making it possible to develop blood tests for early diagnosis.
"This work brings us closer to detecting and diagnosing patients with Parkinson's much earlier than is currently possible. It allows us to study the mechanisms that drive the disease and, in the long term, could lead to treatments that slow or even halt disease progression," says Loge Nilsen.
The study is published in NPJ Parkinson's Disease.
Early Parkinson's revealed by the cells' stress response
The signature reflects a stress response in the cells: they are trying to compensate for biological processes that are beginning to fail. When cells detect threats, they prioritise repair and protection and put other functions temporarily on hold.
According to Loge Nilsen, this functions as a of self-defence strategy that counteracts harmful processes.
"We see this stress response in the early phases of Parkinson's, before motor symptoms become visible. When the disease is established and the diagnosis is made, this stress response is no longer active. At that point, this self-defence strategy is no longer sufficient to prevent disease progression," she explains.
Signs of Parkinson's appear 10-20 years before diagnosis
The researchers discovered that traces of these biological processes are present only for a limited period. They were found exclusively in the early, so-called prodromal phase of Parkinson's, often 10 to 20 years before motor symptoms such as tremors and stiffness occur.
These traces were not found in patients with established Parkinson's, nor in healthy control participants, indicating that the processes are most relevant at the very beginning of the disease course.
"This means we have identified an important window of opportunity that could be crucial for detecting the disease early," says researcher Nicola Montaldo at UiO and OUS.
Why early treatment matters in neurological diseases
This window of opportunity also makes it particularly interesting to study these mechanisms further in the search for medicines that can slow or halt Parkinson's.
"If we can study the mechanisms while they are active, this can provide important information on how they can be stopped, and which medicines may be effective," says Loge Nilsen.
For neurological diseases such as Parkinson's, starting treatment early is especially important.
"Clinical trials usually begin once the patient has been diagnosed. But if you want to treat a disease that affects nerve cells, you need to have enough nerve cells left when treatment starts," she points out.
Michael J. Fox collaboration offers new hope for early detection research
To identify the blood signature, the researchers used data from the Parkinson's Progression Markers Initiative (PPMI), a large international study supported by the Michael J. Fox Foundation. They analysed three groups: people in the early, prodromal phase, patients with established Parkinson's, and healthy controls.
"The prodromal phase is a broad and somewhat difficult category to define. However, the datasets contain samples from people in this phase, which we have been able to analyse," says Loge Nilsen.
Using machine learning and other advanced methods, the researchers identified a clear pattern in the biological processes in people in the early phase of the disease.
"Machine learning is particularly good at recognising patterns that may be difficult for us to see, and at detecting relationships in a slightly different way from what our logical thinking can predict," she says.
A blood test for Parkinson's within five years?
The researchers have studied mechanisms underlying Parkinson's disease for many years. The findings were first observed in the tiny animal model worm C. elegans, then reproduced in human cells, and finally confirmed in the PPMI dataset.
The next step is to understand exactly how these early mechanisms work. Among other things, the researchers will use data from both Norwegian and British cohorts to validate their findings, and to develop tools to make the signature easier to detect.
"We are now working towards creating a diagnostic test that can be used on patient samples. Treatment can then begin while the patient is still functioning well," explains Montaldo.
Such a test may be possible within the next few years.
"The test must still be developed, tested and validated before it can be used in clinical practice. But with adequate funding and access to biological samples, we hope that a test could be ready for broader trials in the health service within five years," he says.
They emphasise, however, that an early detection test will also be most useful if medicines exist that can slow the course of the disease.
Reference
Anwer, D., Montaldo, N.P., Novoa-del-Toro, E.M. et al. Longitudinal assessment of DNA repair signature trajectory in prodromal versus established Parkinson's disease. npj Parkinsons Dis. 11, 349 (2025). https://doi.org/10.1038/s41531-025-01194-7
About the study
The study is led by Hilde Loge Nilsen and Associate Professor Annikka Polster at Chalmers University of Technology in Sweden.
The research is funded by Chalmers Health Engineering Area of Advance in Sweden, The Michael J. Fox Foundation, The Research Council of Norway, The National Academic Infrastructure for Supercomputing (NAISS) in Sweden, and The Swedish Research Council.
