Editors' ChoiceParkinson’s Disease

A QuIC possibility for the diagnosis of Parkinson’s disease

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Science Translational Medicine  21 Feb 2018:
Vol. 10, Issue 429, eaat3168
DOI: 10.1126/scitranslmed.aat3168

Abstract

α-Synuclein seeding activity can be measured quickly and might prove useful for the diagnosis of α-synucleinopathies.

A reliable early or presymptomatic diagnostic test remains a holy grail for most neurogenerative diseases. The ideal diagnostic test should be fast, specific, highly sensitive and minimally invasive, allowing detection of disease at an early stage. α-Synucleinopathies (including Parkinson’s disease and dementia with Lewy bodies) are a family of neurodegenerative disorders characterized by accumulation of α-synuclein within the brain. Currently, definitive diagnosis is often difficult in the early phases of neurodegeneration, when many symptoms and biochemical changes are not disease-specific.

The analysis of seeding activity, the capacity of certain proteins to start a chain reaction that recruits more of themselves into detectible structures, has provided a possible way to distinguish specific disease signatures in patients presenting with early signs of neurodegeneration. Groveman et al. have adapted a strategy originally developed for diagnosing prion disease, real-time quaking-induced conversion (RT-QuIC), into an “ultra-sensitive,” fast diagnostic assay for α-synucleinopathies. The new αSynuclein RT-QuIC is quoted as having 93% diagnostic sensitivity and 100% specificity and was shown to specifically detect early symptomatic patients in a small cohort. The key to the assay performance lies in the substrate: an α-synuclein preparation especially sensitive to the seeding activity of the disease-associated α-synuclein that is able to quickly aggregate into the assay-detectable structures on meeting a seed. These properties allow rapid amplification of the signal permitting detection of very low amounts of seed.

To be effective, therapeutic strategies must be disease-specific and start as early as possible. The rapid and highly specific test developed here might help to improve the quality of life in patients with neurodegenerative disorders. In addition to offering an opportunity for early diagnosis, the development of this assay offers some further thoughts for the future. With the assay principle now applied to three families of neurodegenerative diseases (prion diseases, tauopathies, and α-synucleinopathies), the potential to target other protein misfolding diseases using their respective signature proteins seems achievable. Additionally, the sensitivity and specificity of this assay suggests that it might have an application monitoring disease-specific changes during therapeutic trials.

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