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, Tugce Guel,Susen Schaake,Alexander Balck,Jannik Prasuhn,Philip Campbell,Huw R. Morris,Anthony H. Schapira,Katja Lohmann,Norbert Brueggemann,Aleksandar Rakovic,Philip Seibler,A. Nazli Basak,Daniela Berg,Christine Klein

ANNALS OF NEUROLOGY（2024）

Univ Hosp Schleswig Holstein Campus Kiel | Univ Lubeck | Univ Sch Med | UCL | Univ Schleswig Holstein

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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.

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Key words

a-Synuclein,Parkinson's Disease

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