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Acta Neuropathol Commun. 2018 Feb 9;6(1):7. doi: 10.1186/s40478-018-0508-2.

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

Author information

1
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
2
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
3
Indiana University School of Medicine, Indianapolis, IN, USA.
4
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
5
Department of Neurosciences, University of California-San Diego, La Jolla, CA, USA. dgalasko@ucsd.edu.
6
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. bcaughey@nih.gov.

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 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.

KEYWORDS:

Alzheimer; Amplification; Cerebrospinal fluid; Diagnosis; Lewy body; PMCA; Parkinson; Prion; RT-QuIC; Synuclein

PMID:
29422107
PMCID:
PMC5806364
DOI:
10.1186/s40478-018-0508-2
[Indexed for MEDLINE]
Free PMC Article

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