Publications

Authors:

Groveman, Bradley R; Orrù, Christina D; Hughson, Andrew G; Raymond, Lynne D; Zanusso, Gianluigi; Ghetti, Bernardino; Campbell, Katrina J; Safar, Jiri; Galasko, Douglas; Caughey, Byron

Title:

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

Year:

2018

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

Sì

Name of journal:

ACTA NEUROPATHOLOGICA COMMUNICATIONS

ISSN of journal:

2051-5960

N° Volume:

6

Number or Folder:

1

Page numbers:

1-10

Keyword:

Alzheimer; amplification; cerebrospinal fluid; diagnosis; Lewy body; PMCA; Parkinson; prion; RT-QuIC; synuclein

Short description of contents:

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' cerebrospinal fluid. These prototypic assays require 5-13 days to perform. Here, we describe an improved α-synuclein real time quaking-induced conversion (αSyn 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 αSynD seeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 μL. These results confirm that αSynD 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.

Web page:

https://doi.org/10.1186/s40478-018-0508-2

Product ID:

100656

Handle IRIS:

11562/973269

Last Modified:

November 12, 2022

Bibliographic citation:

Groveman, Bradley R; Orrù, Christina D; Hughson, Andrew G; Raymond, Lynne D; Zanusso, Gianluigi; Ghetti, Bernardino; Campbell, Katrina J; Safar, Jiri; Galasko, Douglas; Caughey, Byron, Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC «ACTA NEUROPATHOLOGICA COMMUNICATIONS» , vol. 6 , n. 1 , 2018 , pp. 1-10

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