α‐Synuclein Pathology in <scp><i>PRKN</i></scp>‐Linked Parkinson's Disease: New Insights from a Blood‐Based Seed Amplification Assay-Reference-Cited by-同舟云学术

α‐Synuclein Pathology in PRKN‐Linked Parkinson's Disease: New Insights from a Blood‐Based Seed Amplification Assay

Published:2024-03-28 Issue:6 Volume:95 Page:1173-1177
ISSN:0364-5134
Container-title:Annals of Neurology
language:en
Short-container-title:Annals of Neurology

Author:

Kluge Annika¹,Borsche Max²³^ORCID,Streubel‐Gallasch Linn²,Gül Tuğçe⁴,Schaake Susen²,Balck Alexander²³^ORCID,Prasuhn Jannik²³^ORCID,Campbell Philip⁵⁶,Morris Huw R.⁵⁶^ORCID,Schapira Anthony H.⁵⁶^ORCID,Lohmann Katja²^ORCID,Brüggemann Norbert²³^ORCID,Rakovic Aleksandar²,Seibler Philip²,Başak A. Nazlı⁴,Berg Daniela¹,Klein Christine²^ORCID

Affiliation:

1. Department of Neurology University Hospital Schleswig‐Holstein Campus Kiel and Kiel University Kiel Germany

2. Institute of Neurogenetics University of Lübeck Lübeck Germany

3. Department of Neurology University Hospital Schleswig‐Holstein Campus Lübeck and University of Lübeck Lübeck Germany

4. Neurodegeneration Research Laboratory (NDAL) Research Center for Translational Medicine (KUTTAM), University School of Medicine Istanbul Turkey

5. Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology, University College London London UK

6. UCL Movement Disorders Center University College London London UK

Abstract

Pathogenic variants in PRKN cause early‐onset Parkinson's disease (PD), while the role of alpha‐synuclein in PRKN‐PD remains uncertain. One study performed a blood‐based alpha‐synuclein seed amplification assay (SAA) in PRKN‐PD, not detecting seed amplification in 17 PRKN‐PD patients. By applying a methodologically different SAA focusing on neuron‐derived extracellular vesicles, we demonstrated alpha‐synuclein seed amplification in 8 of 13 PRKN‐PD patients, challenging the view of PRKN‐PD as a non‐synucleinopathy. Moreover, we performed blinded replication of the neuron‐derived extracellular vesicles‐dependent SAA in idiopathic PD patients and healthy controls. In conclusion, blood‐based neuron‐derived extracellular vesicles‐dependent SAA represents a promising biomarker to elucidate the underpinnings of (monogenic) PD. ANN NEUROL 2024;95:1173–1177

Funder

Deutsche Forschungsgemeinschaft

Michael J. Fox Foundation for Parkinson's Research

Else Kröner-Fresenius-Stiftung

Horizon 2020 Framework Programme

Publisher

Wiley

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.26917

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