The pathological form of a-synuclein (a-syn) is transmitted through neural circuits in the brains of Parkinson disease (PD) patients and amplifies misfolded a-syn, further forming intracellular deposits. However, the details of a-syn pre-formed fibrils (PFFs) transmission in vivo have not been fully elucidated. By inoculating Quantum dots (QD)-labeled a-syn PFFs (QD-a-syn PFFs) into the unilateral striatum, we detected QD-a-syn PFFs in brain homogenates obtained from the ipsilateral and contralateral sides of the inoculated site and further obtained QD-a-syn PFFs enriched-particles with fluorescence-activated organelle sorting. Proteomic analysis suggested that QD-a-syn PFFs-enriched particles in the contralateral side were associated with component proteins of synapse. In contrast, QD-a-syn PFFs-enriched particles in the ipsilateral side were associated with proteins belonging to ER components. Immunostaining of brain sections confirmed that QD-a-syn PFFs in the contralateral side were co-localized with synaptic vesicle marker proteins in the cortex and striatum. Additionally, QD-a-syn PFFs in the ipsilateral side were more co-localized with ER marker proteins compared to the contralateral side. These results correspond to proteomic analysis. This study provides potential candidates for the subcellular localization of a-syn PFFs in vivo during the dissemination phase of seeds. These subcellular compartments could be involved in the transmission of seeds.

a-突触核蛋白 (a-syn) 的病理形式通过帕金森病 (PD) 患者大脑中的神经回路传播并放大错误折叠的 a-syn，进一步形成细胞内沉积物。然而，a-syn 预形成原纤维 (PFFs)体内传输的细节尚未完全阐明。通过将量子点 (QD) 标记的 a-syn PFFs (QD-a-syn PFFs) 接种到单侧纹状体中，我们在从接种部位的同侧和对侧获得的脑匀浆中检测到 QD-a-syn PFFs，并进一步获得具有荧光激活细胞器分选的 QD-a-syn PFFs 富集粒子。蛋白质组学分析表明，对侧富含 QD-a-syn PFF 的颗粒与突触的组成蛋白相关。相比之下，同侧富含 QD-a-syn PFF 的颗粒与属于 ER 成分的蛋白质相关。脑切片的免疫染色证实对侧的 QD-a-syn PFFs 与皮质和纹状体中的突触囊泡标记蛋白共定位。此外，与对侧相比，同侧的 QD-a-syn PFF 与 ER 标记蛋白更共定位。这些结果对应于蛋白质组学分析。这项研究为 a-syn PFFs 的亚细胞定位提供了潜在的候选者在种子传播阶段在体内。这些亚细胞区室可能参与种子的传播。