Summary: Researchers have identified a biomarker in spinal fluid that can detect Parkinson’s disease in its early stages with over 90% accuracy. Using a patented immuno-infrared sensor (iRS) technology, they measured the misfolding of the alpha-synuclein (αSyn) protein, a key driver of the disease.
Early diagnosis is crucial, as clinical symptoms usually appear only after severe and irreversible brain damage. Beyond diagnosis, the platform could also accelerate the development and validation of new Parkinson’s therapies.
Key Facts:
- Early Detection: Misfolded alpha-synuclein (αSyn) in spinal fluid predicts Parkinson’s with over 90% sensitivity and specificity.
- Advanced Technology: The iRS platform detects protein misfolding, a method also validated in Alzheimer’s diagnostics.
- Therapeutic Potential: The biomarker may aid in developing and testing new Parkinson’s treatments by monitoring disease progression.
Source: RUB
Parkinson’s disease is a neurodegenerative disorder that is usually diagnosed in its late stage on the basis of clinical symptoms, mainly motor disorders.
By this point, however, the brain is already severely and irreparably damaged. Moreover, diagnosis is difficult and often incorrect because the disease takes many forms and symptoms overlap with other disorders.
Researchers from the PRODI Center for Protein Diagnostics at Ruhr University Bochum, Germany, and the biotech company betaSENSE have now discovered a biomarker in the spinal fluid that facilitates a reliable diagnosis at an early stage and can shed light on the progression of the disease and the effect of a therapy.
They report their findings in the journal EMBO Molecular Medicine on April 25, 2025.
Parkinson’s disease – an unstoppable condition
Parkinson’s disease is characterized by the loss of dopaminergic nerve cells in the brain, which usually leads to increasing motor impairments as the symptoms progress. Dopamine supplements can compensate for the loss and temporarily alleviate the symptoms.
The misfolding of the key protein alpha-synuclein (αSyn) from α-helical structures to β-sheet-rich structures plays a crucial role in the development of Parkinson’s disease.
“These misfoldings make the protein sticky, leading to the formation of larger complexes, so-called oligomers. The oligomers then produce long fibrillar filaments and cause the aggregation of these filaments into macroscopically large Lewy bodies in the brain,” explains Professor Klaus Gerwert, founding and managing director at PRODI and CEO of betaSENSE.
Advanced platform technology
In two independent clinical cohorts with a total of 134 participants, the Bochum-based researchers showed that, with a sensitivity and specificity of well over 90 percent, this misfolding of αSyn in body-fluids is a viable biomarker for the diagnosis of Parkinson’s disease.
The research was conducted using cerebrospinal fluid samples from patients at the Parkinson’s centers in Bochum (St. Josef Hospital, Professor Lars Tönges, Professor Ralf Gold) and Kassel (Paracelsus-Elena-Klinik, Dr. Sandrina Weber, Professor Brit Mollenhauer).
The measurements were carried out using the patented iRS (immuno-infrared sensor) technology from betaSENSE GmbH.
betaSENSE has already successfully implemented the iRS technology for diagnosing Alzheimer’s disease. In this case, it was shown that the misfolding of the biomarker Aβ can indicate the risk of Alzheimer’s dementia at a later stage with high accuracy up to 17 years before clinical diagnosis.
“We have now transferred this approach to Parkinson’s for the misfolding of αSyn,” stresses Klaus Gerwert.
Development of Parkinson’s drugs
In addition to diagnostic applications, the technology can also help to develop new active substances and prove their efficacy in clinical trials.
About this Parkinson’s disease research news
Author: Julia Weiler
Source: RUB
Contact: Julia Weiler – RUB
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Alpha-synuclein Misfolding as Fluid Biomarker for Parkinson’s Disease Measured with the iRS Platform” by Klaus Gerwert et al. EMBO Molecular Medicine
Abstract
Alpha-synuclein Misfolding as Fluid Biomarker for Parkinson’s Disease Measured with the iRS Platform
Misfolding and aggregation of alpha-synuclein (αSyn) play a key role in the pathophysiology of Parkinson’s disease (PD). Despite considerable advances in diagnostics, an early and differential diagnosis of PD still represents a major challenge.
We innovated the immuno-infrared sensor (iRS) platform for measuring αSyn misfolding. We analyzed cerebrospinal fluid (CSF) from two cohorts comprising PD cases, atypical Parkinsonian disorders, and disease controls.
We obtained an AUC of 0.90 (n = 134, 95% CI 0.85–0.96) for separating PD/MSA from controls by determination of the αSyn misfolding by iRS. Using two thresholds divided individuals as unaffected/affected by misfolding with an intermediate area in between.
Comparing the affected/unaffected cases, controls versus PD/MSA cases were classified with 97% sensitivity and 92% specificity.
The spectral data revealed misfolding from an α-helical/random-coil αSyn in controls to β-sheet enriched αSyn in PD and MSA cases. Moreover, a first subgroup analysis implied the potential for patient stratification in clinically overlapping cases.
The iRS, directly measuring all αSyn conformers, is complementary to the αSyn seed-amplification assays (SAAs), which however only amplify seeding competent conformers.
