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Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease

BACKGROUND: PD diagnosis is based primarily on clinical criteria and can be inaccurate. Biological markers, such as α‐synuclein aggregation, that reflect ongoing pathogenic processes may increase diagnosis accuracy and allow disease progression monitoring. Though α‐synuclein aggregation assays have...

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Autores principales: Kang, Un Jung, Boehme, Amelia K., Fairfoul, Graham, Shahnawaz, Mohammad, Ma, Thong Chi, Hutten, Samantha J., Green, Alison, Soto, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519150/
https://www.ncbi.nlm.nih.gov/pubmed/30840785
http://dx.doi.org/10.1002/mds.27646
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author Kang, Un Jung
Boehme, Amelia K.
Fairfoul, Graham
Shahnawaz, Mohammad
Ma, Thong Chi
Hutten, Samantha J.
Green, Alison
Soto, Claudio
author_facet Kang, Un Jung
Boehme, Amelia K.
Fairfoul, Graham
Shahnawaz, Mohammad
Ma, Thong Chi
Hutten, Samantha J.
Green, Alison
Soto, Claudio
author_sort Kang, Un Jung
collection PubMed
description BACKGROUND: PD diagnosis is based primarily on clinical criteria and can be inaccurate. Biological markers, such as α‐synuclein aggregation, that reflect ongoing pathogenic processes may increase diagnosis accuracy and allow disease progression monitoring. Though α‐synuclein aggregation assays have been published, reproducibility, standardization, and validation are key challenges for their development as clinical biomarkers. OBJECTIVE: To cross‐validate two α‐synuclein seeding aggregation assays developed to detect pathogenic oligomeric α‐synuclein species in CSF using samples from the same PD patients and healthy controls from the BioFIND cohort. METHODS: CSF samples were tested by two independent laboratories in a blinded fashion. BioFIND features standardized biospecimen collection of clinically typical moderate PD patients and nondisease controls. α‐synuclein aggregation was measured by protein misfolding cyclic amplification (Soto lab) and real‐time quaking‐induced conversion (Green lab). Results were analyzed by an independent statistician. RESULTS: Measuring 105 PD and 79 healthy control CSF samples, these assays showed 92% concordance. The areas under the curve from receiver operating characteristic curve analysis for the diagnosis of PD versus healthy controls were 0.93 for protein misfolding cyclic amplification, 0.89 for real‐time quaking‐induced conversion, and 0.95 when considering only concordant assay results. Clinical characteristics of false‐positive and ‐negative subjects were not different from true‐negative and ‐positive subjects, respectively. CONCLUSIONS: These α‐synuclein seeding aggregation assays are reliable and reproducible for PD diagnosis. Assay parameters did not correlate with clinical parameters, including disease severity or duration. This assay is highly accurate for PD diagnosis and may impact clinical practice and clinical trials. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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spelling pubmed-65191502019-05-21 Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease Kang, Un Jung Boehme, Amelia K. Fairfoul, Graham Shahnawaz, Mohammad Ma, Thong Chi Hutten, Samantha J. Green, Alison Soto, Claudio Mov Disord Research Articles BACKGROUND: PD diagnosis is based primarily on clinical criteria and can be inaccurate. Biological markers, such as α‐synuclein aggregation, that reflect ongoing pathogenic processes may increase diagnosis accuracy and allow disease progression monitoring. Though α‐synuclein aggregation assays have been published, reproducibility, standardization, and validation are key challenges for their development as clinical biomarkers. OBJECTIVE: To cross‐validate two α‐synuclein seeding aggregation assays developed to detect pathogenic oligomeric α‐synuclein species in CSF using samples from the same PD patients and healthy controls from the BioFIND cohort. METHODS: CSF samples were tested by two independent laboratories in a blinded fashion. BioFIND features standardized biospecimen collection of clinically typical moderate PD patients and nondisease controls. α‐synuclein aggregation was measured by protein misfolding cyclic amplification (Soto lab) and real‐time quaking‐induced conversion (Green lab). Results were analyzed by an independent statistician. RESULTS: Measuring 105 PD and 79 healthy control CSF samples, these assays showed 92% concordance. The areas under the curve from receiver operating characteristic curve analysis for the diagnosis of PD versus healthy controls were 0.93 for protein misfolding cyclic amplification, 0.89 for real‐time quaking‐induced conversion, and 0.95 when considering only concordant assay results. Clinical characteristics of false‐positive and ‐negative subjects were not different from true‐negative and ‐positive subjects, respectively. CONCLUSIONS: These α‐synuclein seeding aggregation assays are reliable and reproducible for PD diagnosis. Assay parameters did not correlate with clinical parameters, including disease severity or duration. This assay is highly accurate for PD diagnosis and may impact clinical practice and clinical trials. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. John Wiley & Sons, Inc. 2019-03-06 2019-04 /pmc/articles/PMC6519150/ /pubmed/30840785 http://dx.doi.org/10.1002/mds.27646 Text en © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kang, Un Jung
Boehme, Amelia K.
Fairfoul, Graham
Shahnawaz, Mohammad
Ma, Thong Chi
Hutten, Samantha J.
Green, Alison
Soto, Claudio
Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease
title Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease
title_full Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease
title_fullStr Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease
title_full_unstemmed Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease
title_short Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease
title_sort comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of parkinson's disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519150/
https://www.ncbi.nlm.nih.gov/pubmed/30840785
http://dx.doi.org/10.1002/mds.27646
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