Researchers Develop Device to Provide Faster PD Diagnostics

The aggregation of a key component of the pathogenesis of Parkinson disease (PD), α-synuclein, has previously been linked to disease onset and progression. At present, there are no disease-modifying therapies available for the treatment of PD, though a therapy that prevents the accumulation of misfolded α-synuclein would be a promising strategy.

A recent study employed the use of a high-throughput ultrasonication-induced amyloid fibrillation assay to amplify and detect α-synuclein aggregates from cerebrospinal fluid (CSF), and investigated the association between seeding activity and clinical indicators. The assay, created by the study investigators and dubbed the HANdai Amyloid Burst Inducer (HANABI), dramatically reduces the time to perform the assay from the estimated 10 days for the shaking-based assays to only several hours.

“This system has the potential to distinguish patients with Parkinson’s disease from controls based on seeding activity of α-synuclein aggregates in cerebrospinal fluid. This tells us that the HANABI device is sensitive enough to have real clinical potential, and supports the idea that α-synuclein aggregation is a marker of the disease,” Hideki Mochizuki MD, PhD, corresponding author of the study and professor at Osaka University said in a statement.

In order to study the ability of the HANABI assay to detect small amounts of α-synuclein aggregates, the researchers tested several models that mimic the CSF of patients with PD. Of note, the seeding activity of CSF was correlated with the uptake of I-meta-iodobenzylguanidine (MIBG, a radiological characteristic in PD), the low uptake of which has been associated with neurodegeneration. This led researchers to believe that the seeding activity in the CSF of patients with PD could signal the progression of Lewy body pathology.

“In conclusion, our results showed that the sonication-based HANABI assay is a very rapid and useful tool to detect α-synuclein aggregates. The seeding activity of CSF was corelated with reduced MIBG uptake, suggesting the possibility that it reflects Lewy body pathology. Further improvement of the control of ultrasonication is needed for the clinical use of the seeding activity of CSF as a biomarker for PD,” wrote the authors.

Reference

Kakuda K, Ikenaka K, Araki K, et al. Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid [published online April 12, 2019]. Sci Rep. nature.com/articles/s41598-019-42399-0.