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

Annika Kluge; Max Borsche; Linn Streubel-Gallasch; Tuğçe Gül; Susen Schaake; Alexander Balck; Jannik Prasuhn; Philip Campbell; Huw R. Morris; Anthony H. Schapira; Katja Lohmann; Norbert Brüggemann; Aleksandar Rakovic; Philip Seibler; A. Nazlı Başak; Daniela Berg; Christine Klein

doi:10.1002/ana.26917

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

Annika Kluge, Max Borsche, Linn Streubel-Gallasch, Tuğçe Gül, Susen Schaake, Alexander Balck, Jannik Prasuhn, Philip Campbell, Huw R. Morris, Anthony H. Schapira, Katja Lohmann, Norbert Brüggemann, Aleksandar Rakovic, Philip Seibler, A. Nazlı Başak, Daniela Berg^*, Christine Klein^*

^*Korrespondierende/r Autor/-in für diese Arbeit

19 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Annals of Neurology
Jahrgang	95
Ausgabenummer	6
Seiten (von - bis)	1173-1177
Seitenumfang	5
ISSN	0364-5134
DOIs	https://doi.org/10.1002/ana.26917
Publikationsstatus	Veröffentlicht - 06.2024

Fördermittel

We thank the participants for generously donating their time and biomaterials. This project was supported by SysMedPD (European Union's Horizon 2020 research and innovation program under grant agreement 668738), Research Unit FOR2488 (DFG), and the EU Joint Programme–Neurodegenerative Disease Research (JPND). Moreover, the study was supported by the Suna and Inan Kıraç Foundation, the Michael J. Fox Foundation (MJFF), and by a grant of the Else Kröner‐Fresenius‐Stiftung (to M.B.).

Träger	Trägernummer
Suna ve İnan Kıraç Vakfı
Else Kröner-Fresenius-Stiftung
EU Joint Programme – Neurodegenerative Disease Research
Deutsche Forschungsgemeinschaft
SysMedPD
Michael J. Fox Foundation for Parkinson's Research
Horizon 2020
Horizon 2020 Framework Programme	668738

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Querschnittsbereich: Medizinische Genetik

DFG-Fachsystematik

2.23-06 Molekulare und zelluläre Neurologie und Neuropathologie

Dokumente

10.1002/ana.26917

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Kluge, A., Borsche, M., Streubel-Gallasch, L., Gül, T., Schaake, S., Balck, A., Prasuhn, J., Campbell, P., Morris, H. R., Schapira, A. H., Lohmann, K., Brüggemann, N., Rakovic, A., Seibler, P., Başak, A. N., Berg, D., & Klein, C. (2024). α-Synuclein Pathology in PRKN-Linked Parkinson's Disease: New Insights from a Blood-Based Seed Amplification Assay. Annals of Neurology, 95(6), 1173-1177. https://doi.org/10.1002/ana.26917

@article{5428952853e54c0e9f9add793221c506,

title = "α-Synuclein Pathology in PRKN-Linked Parkinson's Disease: New Insights from a Blood-Based Seed Amplification Assay",

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.",

author = "Annika Kluge and Max Borsche and Linn Streubel-Gallasch and Tuğ{\c c}e G{\"u}l and Susen Schaake and Alexander Balck and Jannik Prasuhn and Philip Campbell and Morris, \{Huw R.\} and Schapira, \{Anthony H.\} and Katja Lohmann and Norbert Br{\"u}ggemann and Aleksandar Rakovic and Philip Seibler and Ba{\c s}ak, \{A. Nazlı\} and Daniela Berg and Christine Klein",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2024",

month = jun,

doi = "10.1002/ana.26917",

language = "English",

volume = "95",

pages = "1173--1177",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley \& Sons Inc.",

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}

Kluge, A, Borsche, M , Streubel-Gallasch, L, Gül, T, Schaake, S, Balck, A , Prasuhn, J, Campbell, P, Morris, HR, Schapira, AH, Lohmann, K , Brüggemann, N , Rakovic, A , Seibler, P, Başak, AN, Berg, D & Klein, C 2024, 'α-Synuclein Pathology in PRKN-Linked Parkinson's Disease: New Insights from a Blood-Based Seed Amplification Assay', Annals of Neurology, Jg. 95, Nr. 6, S. 1173-1177. https://doi.org/10.1002/ana.26917

TY - JOUR

T1 - α-Synuclein Pathology in PRKN-Linked Parkinson's Disease

T2 - New Insights from a Blood-Based Seed Amplification Assay

AU - Kluge, Annika

AU - Borsche, Max

AU - Streubel-Gallasch, Linn

AU - Gül, Tuğçe

AU - Schaake, Susen

AU - Balck, Alexander

AU - Prasuhn, Jannik

AU - Campbell, Philip

AU - Morris, Huw R.

AU - Schapira, Anthony H.

AU - Lohmann, Katja

AU - Brüggemann, Norbert

AU - Rakovic, Aleksandar

AU - Seibler, Philip

AU - Başak, A. Nazlı

AU - Berg, Daniela

AU - Klein, Christine

PY - 2024/6

Y1 - 2024/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85189504866

U2 - 10.1002/ana.26917

DO - 10.1002/ana.26917

M3 - Journal articles

C2 - 38546204

AN - SCOPUS:85189504866

SN - 0364-5134

VL - 95

SP - 1173

EP - 1177

JO - Annals of Neurology

JF - Annals of Neurology

IS - 6

ER -

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

Abstract

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UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

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