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

Annika KlugeMax BorscheLinn Streubel-GallaschTuğçe GülSusen SchaakeAlexander BalckJannik PrasuhnPhilip CampbellHuw R MorrisAnthony H V SchapiraKatja LohmannNorbert BrüggemannAleksandar RakovicPhilip SeiblerA Nazlı BaşakDaniela BergChristine Klein
Published in: Annals of neurology (2024)
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.
Keyphrases
  • end stage renal disease
  • early onset
  • newly diagnosed
  • ejection fraction
  • peritoneal dialysis
  • prognostic factors
  • high throughput
  • randomized controlled trial
  • gene expression
  • nucleic acid
  • patient reported
  • copy number