Many human diseases can be detected and diagnosed using biomarkers in the blood or other bodily fluids. It is different with Parkinson’s disease: To date, there is no such biomarker in the clinic that indicates this neurodegenerative disease.
A team led by ETH professor Paola Picotti could now help to close this gap. In a study just published in the journal Nature Structural and Molecular Biologythe researchers present 76 proteins that could serve as biomarkers to detect Parkinson’s disease.
Different protein structure
What is unique about this study is that while the potential biomarker proteins are found in both healthy and diseased individuals, their molecules are present in different shapes (or structures) in each of the two groups. It is not the presence of certain proteins that indicates the disease, but the form they have taken. This is the first time scientists have shown that an analysis of the structures of all proteins in a body fluid can identify potential biomarkers of disease.
In the next step, the markers found will be tested extensively and verified in larger patient groups. This means that these candidates are not yet available for clinical diagnosis. “But from what we’ve seen so far, they’re actually a very strong predictor of the disease.” Therefore, I am confident that this idea of structural biomarkers will be confirmed,” says Natalie de Souza, senior scientist in Paola Picotti’s group and one of the co-authors of the study.
Measure structural changes
In their study, the ETH researchers examined the CSF of 50 healthy people and 50 Parkinson’s patients. The sample material was made available to them by Dutch clinicians.
To search for biomarkers, the scientists used a special method for measuring the proteome (i.e. all proteins in a sample) called LiP-MS, which can measure structural changes in proteins and show exactly where the changes are located are. Conventional proteome measurements usually only record the different protein types and their amounts, but not structural changes.
Because the structure of proteins is closely linked to their functions (or malfunctions), the researchers hypothesized that people with Parkinson’s and healthy individuals have different shapes of some proteins.
The present study is the first time the researchers have successfully applied the method to a disease.
further refine the analysis
In further steps, the researchers want to further improve the LiP-MS method in order to strengthen the biomarker signal and thus increase the sensitivity with which the disease can be detected. In addition, the scientists want to test the new biomarkers to assess how specifically they recognize Parkinson’s disease or whether there may be overlaps with other neurodegenerative diseases such as Alzheimer’s disease. In the future, the researchers also want to use their method to determine subtypes of Parkinson’s disease and make more accurate predictions about the course of the disease.
It is still uncertain which clinically meaningful diagnostics this could lead to. De Souza estimates that a future testing strategy could be based on antibodies that would distinguish between healthy and diseased protein structures. The regular use of mass spectrometers in the clinical environment is possible in principle, but a major challenge.
Materials provided by ETH Zurich. Originally written by Peter Rüegg. Note: Content can be edited for style and length.