Spinal Fluid Biomarker for Parkinson’s Disease Offers Early and Accurate Diagnosis

Parkinson’s disease is a neurodegenerative condition typically diagnosed at an advanced stage based on clinical symptoms, primarily motor disorders. However, by this time, the brain has already undergone significant and irreversible damage. Additionally, diagnosis can be challenging and often inaccurate because the disease manifests in various forms, with symptoms overlapping those of other disorders. Researchers have now identified a biomarker in spinal fluid that enables a reliable diagnosis at an earlier stage and provides insights into disease progression and the effects of therapy.

Parkinson’s disease is marked by the loss of dopaminergic nerve cells in the brain, leading to progressively worsening motor impairments. While dopamine supplements can temporarily compensate for the loss and alleviate symptoms, they do not address the underlying cause. A key factor in the development of Parkinson’s disease is the misfolding of the protein alpha-synuclein (αSyn) from α-helical structures to β-sheet-rich structures. These misfoldings cause the protein to become sticky, leading to the formation of larger complexes known as oligomers. The oligomers then form long fibrillar filaments, which aggregate into large Lewy bodies in the brain.

Image: Researchers showed that misfolding of alpha-synuclein can accurately detect Parkinson’s in CSF (Photo courtesy of Ruhr University Bochum)

In two independent clinical cohorts comprising a total of 134 participants, researchers from the PRODI Center for Protein Diagnostics at Ruhr University Bochum (Bochum, Germany) and its spin-off biotech company betaSENSE (Bochum, Germany) demonstrated that the misfolding of αSyn in bodily fluids is a reliable biomarker for diagnosing Parkinson’s disease, with sensitivity and specificity exceeding 90 percent. The study, which used cerebrospinal fluid samples from patients at Parkinson’s centers in Germany, employed betaSENSE’s patented iRS (immuno-infrared sensor) technology. This technology has already been successfully applied in diagnosing Alzheimer’s disease. The findings, published in EMBO Molecular Medicine, revealed that misfolding of the biomarker Aβ can predict the risk of Alzheimer’s dementia with high accuracy, up to 17 years before a clinical diagnosis. Beyond diagnostic applications, this technology can also aid in the development of new therapeutic agents and validate their effectiveness in clinical trials.

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