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. 2024 Jun;95(6):1173-1177.
doi: 10.1002/ana.26917. Epub 2024 Mar 28.

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

Annika Kluge  1 , Max Borsche  2   3 , Linn Streubel-Gallasch  2 , Tuğçe Gül  4 , Susen Schaake  2 , Alexander Balck  2   3 , Jannik Prasuhn  2   3 , Philip Campbell  5   6 , Huw R Morris  5   6 , Anthony H Schapira  5   6 , Katja Lohmann  2 , Norbert Brüggemann  2   3 , Aleksandar Rakovic  2 , Philip Seibler  2 , A Nazlı Başak  4 , Daniela Berg  1 , Christine Klein  2
Affiliations

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

Annika Kluge et al. Ann Neurol. 2024 Jun.

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.

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