Asia-Pacific Biotech News

A More Accurate and Precise Diagnostic Tool for Neurodegenerative Disorders

By taking advantage of the unique properties of the protein behind several neurodegenerative disorders, researchers have developed a novel diagnostic tool that will improve clinical diagnosis and thus help people at risk of these disorders.

Parkinson’s Disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MLA) are examples of synucleinopathy—neurodegenerative disorders characterised by the abnormal aggregation of α-synuclein proteins. This harmful protein aggregation occurs exponentially through a seeding mechanism, whereby a small number of misfolded α-synuclein proteins initiate the misfolding of associated proteins, thus forming toxic clumps in the brain. Currently, there are no appropriate blood or laboratory tests to diagnose these disorders; diagnoses are dependent on patient symptoms and a neurological examination conducted by a neurologist. Fortunately, the results of a recent study published in Nature Medicine may prove to be a gamechanger.

Previous studies on α-synuclein proteins using molecular amplification methods have revealed that synucleinopathy-specific α-synuclein proteins can be found in the blood plasma and various tissues. In addition, previous imaging studies were able to reveal the abnormal structures of α-synuclein proteins found in the blood plasma. These two properties suggest the potential use of α-synuclein proteins as a biomarker for synucleinopathy. By modifying the research protocols of the first study, researchers from Japan, led by Associate Professor Ayami Okuzumi, Professor Nobutaka Hattori, and Senior Associate Professor Taku Hatano from Jutendo University School of Medicine, and Senior Assistant Professor Gen Matsumoto from Nagaski University School of Medicine, were able to develop a new testing method that can efficiently detect α-synuclein protein levels in a patient’s blood serum.

The modified assay, called immunoprecipitation-based real-time quacking-induced conversion (IP/RT-QuIC), combines a variety of molecular techniques and works by taking advantage of α-synuclein proteins’ seeding property. In this assay, the α-synuclein seeds are first isolated from the patients’ blood serum by immunoprecipitation—the process of separating proteins by using an antibody that binds specifically to the target protein. Next, the α-synuclein proteins are amplified by vigorous shaking. The researchers noted that this method is highly sensitive and can detect α-synuclein concentrations as low as 1000 pg/ml.

Aside from developing a novel diagnostic tool for synucleinopathy, the researchers also went on to study the structural properties of the amplified α-synuclein proteins in patient samples using transmission electron microscopy (TEM). They observed that α-synuclein seed structures differ according to the type of synucleinopathy. For example, α-synuclein proteins in PD have paired filaments while MSA-related proteins can have either twisted or straight filaments. To confirm this finding, they induced amplified α-synuclein proteins in human tissue culture and mouse brains. Again, they found that α-synuclein aggregates displayed different disease-specific structures. Hence, the authors concluded that TEM with IP/RT-QuIC should be combined to more accurately diagnose synucleinopathy down to its specific disorders.

Overall, the study proved that α-synuclein can seed in the blood plasma and that different α-synuclein conformations lead to different neurodegenerative diseases. Hence, the novel IP/RT-QuIC assay may serve as a high-performance biomarker to diagnose synucleinopathy. For the healthcare industry, this novel diagnostic method means that a neurology expert is no longer necessary to diagnose synucleinopathy. Therefore, more patients can be diagnosed with precision and receive the appropriate treatments at an earlier stage. In addition, the authors believe that the simplicity of this new assay will enable the establishment of more personalised therapy options for people suffering from synucleinopathy. [APBN]

Source: Okuzumi et al. (2023). Propagative α-synuclein seeds as serum biomarkers for synucleinopathies. Nature Medicine. https://doi.org/10.1038/s41591-023-02358-9