Interlaboratory validation of cerebrospinal fluid α-synuclein quantification in the diagnosis of sporadic Creutzfeldt-Jakob disease

Niels Kruse, Amanda Heslegrave, Vandana Gupta, Martha Foiani, Anna Villar-Piqué, Matthias Schmitz, Sylvain Lehmann, Charlotte Teunissen, Kaj Blennow, Henrik Zetterberg, Brit Mollenhauer, Inga Zerr, Franc Llorens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods: Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non–Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories. Results: A sensitivity of 93% and a specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23%, and the intralaboratory coefficient of variations ranged 2.70%–11.39%. Overall, 97% of samples were correctly diagnosed. Discussion: The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease.
Original languageEnglish
Pages (from-to)461-470
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume10
DOIs
Publication statusPublished - 2018

Cite this

Kruse, Niels ; Heslegrave, Amanda ; Gupta, Vandana ; Foiani, Martha ; Villar-Piqué, Anna ; Schmitz, Matthias ; Lehmann, Sylvain ; Teunissen, Charlotte ; Blennow, Kaj ; Zetterberg, Henrik ; Mollenhauer, Brit ; Zerr, Inga ; Llorens, Franc. / Interlaboratory validation of cerebrospinal fluid α-synuclein quantification in the diagnosis of sporadic Creutzfeldt-Jakob disease. In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. 2018 ; Vol. 10. pp. 461-470.
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title = "Interlaboratory validation of cerebrospinal fluid α-synuclein quantification in the diagnosis of sporadic Creutzfeldt-Jakob disease",
abstract = "Introduction: Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods: Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non–Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories. Results: A sensitivity of 93{\%} and a specificity of 96{\%} were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23{\%}, and the intralaboratory coefficient of variations ranged 2.70{\%}–11.39{\%}. Overall, 97{\%} of samples were correctly diagnosed. Discussion: The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease.",
author = "Niels Kruse and Amanda Heslegrave and Vandana Gupta and Martha Foiani and Anna Villar-Piqu{\'e} and Matthias Schmitz and Sylvain Lehmann and Charlotte Teunissen and Kaj Blennow and Henrik Zetterberg and Brit Mollenhauer and Inga Zerr and Franc Llorens",
year = "2018",
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Interlaboratory validation of cerebrospinal fluid α-synuclein quantification in the diagnosis of sporadic Creutzfeldt-Jakob disease. / Kruse, Niels; Heslegrave, Amanda; Gupta, Vandana; Foiani, Martha; Villar-Piqué, Anna; Schmitz, Matthias; Lehmann, Sylvain; Teunissen, Charlotte; Blennow, Kaj; Zetterberg, Henrik; Mollenhauer, Brit; Zerr, Inga; Llorens, Franc.

In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, Vol. 10, 2018, p. 461-470.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Interlaboratory validation of cerebrospinal fluid α-synuclein quantification in the diagnosis of sporadic Creutzfeldt-Jakob disease

AU - Kruse, Niels

AU - Heslegrave, Amanda

AU - Gupta, Vandana

AU - Foiani, Martha

AU - Villar-Piqué, Anna

AU - Schmitz, Matthias

AU - Lehmann, Sylvain

AU - Teunissen, Charlotte

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Mollenhauer, Brit

AU - Zerr, Inga

AU - Llorens, Franc

PY - 2018

Y1 - 2018

N2 - Introduction: Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods: Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non–Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories. Results: A sensitivity of 93% and a specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23%, and the intralaboratory coefficient of variations ranged 2.70%–11.39%. Overall, 97% of samples were correctly diagnosed. Discussion: The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease.

AB - Introduction: Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods: Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non–Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories. Results: A sensitivity of 93% and a specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23%, and the intralaboratory coefficient of variations ranged 2.70%–11.39%. Overall, 97% of samples were correctly diagnosed. Discussion: The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30294658

U2 - 10.1016/j.dadm.2018.06.005

DO - 10.1016/j.dadm.2018.06.005

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JO - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

JF - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

SN - 2352-8729

ER -