Revolutionary Blood Test Developed for Synucleinopathies – Unveiling the Origins of Neurodegeneration

A groundbreaking blood test called IP/RT-QuIC has been created by scientists to identify α-synuclein seeds in the serum of synucleinopathy patients. This innovative assay allows for the early and accurate diagnosis of synucleinopathies such as Parkinson’s disease, leading to personalized treatments. Japanese researchers spearheaded the development of this test, which detects clusters of abnormally folded α-synuclein proteins, known as seeds, in the blood. These seeds are responsible for triggering the formation of larger clumps, resulting in a class of neurodegenerative disorders referred to as synucleinopathies.

The newly devised assay offers several advantages. It exhibits high sensitivity, simplicity in administration, and delivers rapid results. Moreover, it can differentiate between various synucleinopathies by detecting structural discrepancies in the amplified seeds. The research received funding from the Japan Agency for Medical Research and Development’s National Research Program for Neurological Disorders and Mental Health.

Synucleinopathies encompass a group of neurodegenerative diseases caused by the abnormal accumulation of α-synuclein, a protein typically found in the brain and neurons. Incorrect folding of α-synuclein leads to the creation of seeds that attract additional α-synuclein proteins, resulting in the formation of larger clumps. Although α-synuclein seeds have been detected in various tissues and the blood of synucleinopathy patients, their potential as a biomarker remains unclear.

The IP/RT-QuIC assay efficiently detects even trace amounts of serum α-synuclein seeds, facilitating the prompt diagnosis of specific neurodegenerative disorders. Credit for this achievement goes to Professor Hattori and his team from Juntendo University School of Medicine.

In a recent study published in Nature Medicine, Associate Professor Ayami Okuzumi, Senior Associate Professor Taku Hatano from Juntendo University School of Medicine, Senior Assistant Professor Gen Matsumoto from Nagasaki University School of Medicine, and Professor Nobutaka Hattori from Juntendo University Faculty of Medicine / RIKEN Center for Brain Science presented a novel assay capable of effectively detecting α-synuclein seeds in a patient’s serum.

Named immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), this assay isolates α-synuclein seeds from the patient’s serum using immunoprecipitation, a technique that separates proteins by employing an antibody specific to the target protein. Subsequently, rapid amplification is achieved through real-time quaking-induced conversion, which involves vigorous shaking. This method boasts exceptional sensitivity, enabling the detection of serum α-synuclein seed concentrations as low as 1000pg/ml. This is particularly significant as most existing diagnostic methods require cerebrospinal fluid for synuclein detection. The study was made available on May 30, 2023.

Sharing the objective of their study, Professor Hattori and his team explain, “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).”

The research team demonstrated the efficient detection of α-synuclein seeds by IP/RT-QuIC in patients with neurodegenerative diseases, distinguishing them from individuals without degenerative diseases (controls). Furthermore, they studied the structural properties of the amplified seeds using transmission electron microscopy (TEM) and