دورية أكاديمية
أعرض في EDS

Accurate Detection of α-Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort.

التفاصيل البيبلوغرافية
العنوان: Accurate Detection of α-Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort.
المؤلفون: Concha-Marambio L; Research and Development Unit, Amprion Inc., San Diego, California, USA., Weber S; Department of Neurology, University Medical Centre Goettingen, Goettingen, Germany.; Paracelsus-Elena-Klinik, Kassel, Germany., Farris CM; Research and Development Unit, Amprion Inc., San Diego, California, USA., Dakna M; Department of Neurology, University Medical Centre Goettingen, Goettingen, Germany., Lang E; Paracelsus-Elena-Klinik, Kassel, Germany., Wicke T; Paracelsus-Elena-Klinik, Kassel, Germany., Ma Y; Research and Development Unit, Amprion Inc., San Diego, California, USA., Starke M; Paracelsus-Elena-Klinik, Kassel, Germany., Ebentheuer J; Paracelsus-Elena-Klinik, Kassel, Germany., Sixel-Döring F; Paracelsus-Elena-Klinik, Kassel, Germany.; Department of Neurology, Philipps University Marburg, Marburg, Germany., Muntean ML; Paracelsus-Elena-Klinik, Kassel, Germany., Schade S; Paracelsus-Elena-Klinik, Kassel, Germany., Trenkwalder C; Paracelsus-Elena-Klinik, Kassel, Germany.; Department of Neurosurgery, University Medical Centre Goettingen, Goettingen, Germany., Soto C; Research and Development Unit, Amprion Inc., San Diego, California, USA.; Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas McGovern Medical School, Houston, Texas, USA., Mollenhauer B; Department of Neurology, University Medical Centre Goettingen, Goettingen, Germany.; Paracelsus-Elena-Klinik, Kassel, Germany.
المصدر: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2023 Apr; Vol. 38 (4), pp. 567-578. Date of Electronic Publication: 2023 Feb 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8610688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8257 (Electronic) Linking ISSN: 08853185 NLM ISO Abbreviation: Mov Disord Subsets: MEDLINE
أسماء مطبوعة: Publication: <2001->: New York, NY : Wiley-Liss
Original Publication: [New York, N.Y.] : Raven Press, [c1986-
مواضيع طبية MeSH: alpha-Synuclein*/cerebrospinal fluid , alpha-Synuclein*/chemistry , Parkinson Disease*/diagnosis , Parkinson Disease*/metabolism , REM Sleep Behavior Disorder*/diagnosis , REM Sleep Behavior Disorder*/metabolism, Humans ; Synucleinopathies/diagnosis
مستخلص: Background: Misfolded α-synuclein (αSyn) aggregates (αSyn-seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn-seeds have been detected in prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD).
Objectives: The objective of this study was to determine the accuracy of the αSyn-seed amplification assay (αS-SAA) in a comprehensively characterized cohort with a high proportion of PD and iRBD CSF samples collected at baseline.
Methods: We used a high-throughput αS-SAA to analyze 233 blinded CSF samples from 206 participants of the DeNovo Parkinson Cohort (DeNoPa) (113 de novo PD, 64 healthy controls, 29 iRBD confirmed by video polysomnography). Results were compared with the final diagnosis, which was determined after up to 10 years of longitudinal clinical evaluations, including dopamine-transporter-single-photon emission computed tomography (DAT-SPECT) at baseline, CSF proteins, Movement Disorder Society-Unified Parkinson's Disease Rating Scale, and various cognitive and nonmotor scales.
Results: αS-SAA detected αSyn-seeds in baseline PD-CSF with 98% accuracy. αSyn-seeds were detected in 93% of the iRBD cases. αS-SAA results showed higher agreement with the final than the initial diagnosis, as 14 patients were rediagnosed as non-αSyn aggregation disorder. For synucleinopathies, αS-SAA showed higher concordance with the final diagnosis than DAT-SPECT. Statistically significant correlations were found between assay parameters and disease progression.
Conclusions: Our results confirm αS-SAA accuracy at the first clinical evaluation when a definite diagnosis is most consequential. αS-SAA conditions reported here are highly sensitive, enabling the detection of αSyn-seeds in CSF from iRBD just months after the first symptoms, suggesting that αSyn-seeds are present in the very early prodromal phase of synucleinopathies. Therefore, αSyn-seeds are clear risk markers for synuclein-related disorders, but not for time of phenoconversion. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
(© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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معلومات مُعتمدة: RF1AG059321 United States NH NIH HHS; RF1AG055053 United States NH NIH HHS; RF1 AG055053 United States AG NIA NIH HHS; U24 AG079685 United States AG NIA NIH HHS; R01 AG061069 United States AG NIA NIH HHS; RF1 AG059321 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: CSF; RBD; early Parkinson's disease; seed amplification assay; α-Synuclein
المشرفين على المادة: 0 (alpha-Synuclein)
تواريخ الأحداث: Date Created: 20230213 Date Completed: 20230421 Latest Revision: 20240402
رمز التحديث: 20240402
مُعرف محوري في PubMed: PMC10153075
DOI: 10.1002/mds.29329
PMID: 36781413
قاعدة البيانات: MEDLINE
الوصف
تدمد:1531-8257
DOI:10.1002/mds.29329