Dataset Information

Rapid and ultra-sensitive quantitation of disease-associated ?-synuclein seeds in brain and cerebrospinal fluid by ?Syn RT-QuIC.

ABSTRACT: The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of ?-synuclein (?SynD) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent ?SynD seed amplification tests have provided the first prototypes for ultrasensitive and specific detection of ?SynD in patients' cerebrospinal fluid. These prototypic assays require 5-13 days to perform. Here, we describe an improved ?-synuclein real time quaking-induced conversion (?Syn RT-QuIC) assay that has similar sensitivity and specificity to the prior assays, but can be performed in 1-2 days with quantitation. Blinded analysis of cerebrospinal fluid from 29 synucleinopathy cases [12 Parkinson's and 17 dementia with Lewy bodies] and 31 non-synucleinopathy controls, including 16 Alzheimer's cases, yielded 93% diagnostic sensitivity and 100% specificity for this test so far. End-point dilution analyses allowed quantitation of relative amounts of ?SynD seeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 ?L. These results confirm that ?SynD seeding activity is present in cerebrospinal fluid. We also demonstrate that it can be rapidly detected, and quantitated, even in early symptomatic stages of synucleinopathy.

SUBMITTER: Groveman BR

PROVIDER: S-EPMC5806364 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC.

Groveman Bradley R BR Orrù Christina D CD Hughson Andrew G AG Raymond Lynne D LD Zanusso Gianluigi G Ghetti Bernardino B Campbell Katrina J KJ Safar Jiri J Galasko Douglas D Caughey Byron B

Acta neuropathologica communications 20180209 1

The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of α-synuclein (αSynD) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent αSynD seed amplification tests have provided the first prototypes for ultrasensitive and specific detection of αSynD in patients' cer ...[more]

PMID: 29422107

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Dataset Information

Rapid and ultra-sensitive quantitation of disease-associated ?-synuclein seeds in brain and cerebrospinal fluid by ?Syn RT-QuIC.

Publications

Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC.

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