High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

Abstract Alpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and...

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Autores principales:	Marco J. Russo, Christina D. Orru, Luis Concha-Marambio, Simone Giaisi, Bradley R. Groveman, Carly M. Farris, Bret Holguin, Andrew G. Hughson, David-Erick LaFontant, Chelsea Caspell-Garcia, Christopher S. Coffey, Jennifer Mollon, Samantha J. Hutten, Kalpana Merchant, Roland G. Heym, Claudio Soto, Byron Caughey, Un Jung Kang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Seed amplification assay Alpha-synuclein Parkinson’s disease RT-QuIC PMCA Synucleinopathy Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/0bfa462724b04d9e816718abf0d9ecbe
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spelling	oai:doaj.org-article:0bfa462724b04d9e816718abf0d9ecbe2021-11-07T12:17:10ZHigh diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease10.1186/s40478-021-01282-82051-5960https://doaj.org/article/0bfa462724b04d9e816718abf0d9ecbe2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40478-021-01282-8https://doaj.org/toc/2051-5960Abstract Alpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories. We compared αSyn-SAA results obtained from three independent laboratories to evaluate reproducibility across methodological variations. We utilized the Parkinson’s Progression Markers Initiative (PPMI) cohort, with DATSCAN data available for comparison, since clinical diagnosis of early de novo PD is critical for neuroprotective trials, which often use dopamine transporter imaging to enrich their cohorts. Blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD), from both baseline and year 3 collections for the PD and HC groups (140 total CSF samples) were analyzed in parallel by each lab according to their own established and optimized αSyn-SAA protocols. The αSyn-SAA results were remarkably similar across laboratories, displaying high diagnostic performance (sensitivity ranging from 86 to 96% and specificity from 93 to 100%). The assays were also concordant for samples with results that differed from clinical diagnosis, including 2 PD patients determined to be clinically inconsistent with PD at later time points. All three assays also detected 2 SWEDD subjects as αSyn-SAA positive who later developed PD with abnormal DAT-SPECT. These multi-laboratory results confirm the reproducibility and value of αSyn-SAA as diagnostic tools, illustrate reproducibility of the assay in expert hands, and suggest that αSyn-SAA has potential to provide earlier diagnosis with comparable or superior accuracy to existing methods.Marco J. RussoChristina D. OrruLuis Concha-MarambioSimone GiaisiBradley R. GrovemanCarly M. FarrisBret HolguinAndrew G. HughsonDavid-Erick LaFontantChelsea Caspell-GarciaChristopher S. CoffeyJennifer MollonSamantha J. HuttenKalpana MerchantRoland G. HeymClaudio SotoByron CaugheyUn Jung KangBMCarticleSeed amplification assayAlpha-synucleinParkinson’s diseaseRT-QuICPMCASynucleinopathyNeurology. Diseases of the nervous systemRC346-429ENActa Neuropathologica Communications, Vol 9, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Seed amplification assay Alpha-synuclein Parkinson’s disease RT-QuIC PMCA Synucleinopathy Neurology. Diseases of the nervous system RC346-429
spellingShingle	Seed amplification assay Alpha-synuclein Parkinson’s disease RT-QuIC PMCA Synucleinopathy Neurology. Diseases of the nervous system RC346-429 Marco J. Russo Christina D. Orru Luis Concha-Marambio Simone Giaisi Bradley R. Groveman Carly M. Farris Bret Holguin Andrew G. Hughson David-Erick LaFontant Chelsea Caspell-Garcia Christopher S. Coffey Jennifer Mollon Samantha J. Hutten Kalpana Merchant Roland G. Heym Claudio Soto Byron Caughey Un Jung Kang High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
description	Abstract Alpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories. We compared αSyn-SAA results obtained from three independent laboratories to evaluate reproducibility across methodological variations. We utilized the Parkinson’s Progression Markers Initiative (PPMI) cohort, with DATSCAN data available for comparison, since clinical diagnosis of early de novo PD is critical for neuroprotective trials, which often use dopamine transporter imaging to enrich their cohorts. Blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD), from both baseline and year 3 collections for the PD and HC groups (140 total CSF samples) were analyzed in parallel by each lab according to their own established and optimized αSyn-SAA protocols. The αSyn-SAA results were remarkably similar across laboratories, displaying high diagnostic performance (sensitivity ranging from 86 to 96% and specificity from 93 to 100%). The assays were also concordant for samples with results that differed from clinical diagnosis, including 2 PD patients determined to be clinically inconsistent with PD at later time points. All three assays also detected 2 SWEDD subjects as αSyn-SAA positive who later developed PD with abnormal DAT-SPECT. These multi-laboratory results confirm the reproducibility and value of αSyn-SAA as diagnostic tools, illustrate reproducibility of the assay in expert hands, and suggest that αSyn-SAA has potential to provide earlier diagnosis with comparable or superior accuracy to existing methods.
format	article
author	Marco J. Russo Christina D. Orru Luis Concha-Marambio Simone Giaisi Bradley R. Groveman Carly M. Farris Bret Holguin Andrew G. Hughson David-Erick LaFontant Chelsea Caspell-Garcia Christopher S. Coffey Jennifer Mollon Samantha J. Hutten Kalpana Merchant Roland G. Heym Claudio Soto Byron Caughey Un Jung Kang
author_facet	Marco J. Russo Christina D. Orru Luis Concha-Marambio Simone Giaisi Bradley R. Groveman Carly M. Farris Bret Holguin Andrew G. Hughson David-Erick LaFontant Chelsea Caspell-Garcia Christopher S. Coffey Jennifer Mollon Samantha J. Hutten Kalpana Merchant Roland G. Heym Claudio Soto Byron Caughey Un Jung Kang
author_sort	Marco J. Russo
title	High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
title_short	High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
title_full	High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
title_fullStr	High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
title_full_unstemmed	High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
title_sort	high diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early parkinson’s disease
publisher	BMC
publishDate	2021
url	https://doaj.org/article/0bfa462724b04d9e816718abf0d9ecbe
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High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

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