Department of Neurology, University Hospital Schleswig-Holstein Campus Kiel and Kiel University, Kiel, Germany.
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Ann Neurol. 2024 Jun;95(6):1173-1177. doi: 10.1002/ana.26917. Epub 2024 Mar 28.
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.
PRKN 中的致病变异可导致早发性帕金森病（PD），而α-突触核蛋白在 PRKN-PD 中的作用尚不确定。一项研究在 PRKN-PD 患者中进行了基于血液的α-突触核蛋白种子扩增检测（SAA），未在 17 名 PRKN-PD 患者中检测到种子扩增。通过应用一种方法学上不同的、侧重于神经元衍生细胞外囊泡的 SAA，我们在 13 名 PRKN-PD 患者中的 8 名中证实了α-突触核蛋白种子扩增，这对 PRKN-PD 作为非突触核蛋白病的观点提出了挑战。此外，我们对特发性 PD 患者和健康对照者进行了基于神经元衍生细胞外囊泡的 SAA 的盲法复制。总之，基于血液的神经元衍生细胞外囊泡依赖性 SAA 代表了一种有前途的生物标志物，可阐明（单基因）PD 的潜在机制。神经病学年鉴 2024；95：1173-1177。
