Researchers at the Juntendo University Research Promotion Center have developed a blood serum assay that can identify specific neurodegenerative diseases by detecting abnormal levels of a protein, called α-synuclein in patient sera.
Blood biomarkers of neurodegeneration are paving the way for non-invasive diagnostics of neurodegenerative disease. A protein known as α-synuclein, acts as a biomarker for synucleinopathies—a group of neurodegenerative diseases caused by abnormal accumulation of the protein, including Parkinson’s disease, Lewy body dementia and multiple system atrophy.
Reporting in Nature Medicine, scientists have now developed a blood assay, known as immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), that is able to efficiently detect α-synuclein in a patient’s serum, potentially eliminating the need for classic invasive testing using cerebrospinal fluid.
The assay works by isolating α-synuclein seeds from the patient’s blood by immunoprecipitation—protein separation with the help of an antibody binding only the protein of interest, followed by amplification induced by vigorous shaking. According to the researchers, the method is highly sensitive, detecting serum α-synuclein seed concentrations as small as 1000 pg/ml.
“In this study, we validated the usefulness of our novel assay system, IP/RT-QuIC, as a diagnostic marker of synucleinopathies. We propose that the fibril morphology of serum α-synuclein seeds and aggregates derived by IP/RT-QuIC can discriminate between Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA),”said Nobutaka Hattori, PhD, professor at Juntendo University Faculty of Medicine and senior author of the study.
The scientists were able to demonstrate that IP/RT-QuIC detected the protein efficiently in patients with neurodegenerative disease and could distinguish them from healthy people. Using transmission electron microscopy, the researchers also determined that the α-synuclein protein structures vary by synucleinopathy—allowing for a more specific diagnosis.
To further confirm their findings, the researchers transduced amplified α-synuclein seeds into a cell line stably expressing GFP-fused human α-synuclein as well as injecting them into mouse brains. According to the scientists, the seeds retained their aggregate forming capacity and their disease-specific structure in both models.
“At present, a neurologist’s consultation is necessary to diagnose synucleinopathies. However, using IP/RTQuIC, a general internist can make the diagnosis. Therefore, more patients with synucleinopathies may be diagnosed with precision and could receive appropriate treatment at an earlier stage.”
“Our new IP/RT-QuIC assay may have many future applications as a biomarker for precise diagnosis and monitoring of treatment of neurodegenerative diseases in clinical trials. This simple diagnostic method will enable establishment of personalized therapy options for synucleinopathies,” Hattori concluded in a press statement.