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^*

^*Corresponding author for this work

16 Citations (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.

Original language	English
Journal	Annals of Neurology
Volume	95
Issue number	6
Pages (from-to)	1173-1177
Number of pages	5
ISSN	0364-5134
DOIs	https://doi.org/10.1002/ana.26917
Publication status	Published - 06.2024

Funding

Funders	Funder number
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

Research Areas and Centers

Research Area: Medical Genetics

DFG Research Classification Scheme

2.23-06 Molecular and Cellular Neurology and Neuropathology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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, vol. 95, no. 6, pp. 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

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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