The contribution of circulatory tau and β-amyloid in Parkinson's disease (PD), especially the cognitive function, remains inconclusive. Extracellular vesicles (EVs) cargo these proteins throughout the bloodstream after they are directly secreted from many cells, including neurons. The present study aims to investigate the role of the plasma EV-borne tau and β-amyloid as biomarkers for cognitive dysfunction in PD by investigating subjects with mild to moderate stage of PD (n = 116) and non-PD controls (n = 46). Plasma EVs were isolated, and immunomagnetic reduction-based immunoassay was used to assess the levels of α-synuclein, tau, and β-amyloid 1-42 (Aβ1-42) within the EVs. Artificial neural network (ANN) models were then applied to predict cognitive dysfunction. We observed no significant difference in plasma EV tau and Aβ1-42 between PD patients and controls. Plasma EV tau was significantly associated with cognitive function. Moreover, plasma EV tau and Aβ1-42 were significantly elevated in PD patients with cognitive impairment when compared to PD patients with optimal cognition. The ANN model used the plasma EV α-synuclein, tau, and Aβ1-42, as well as the patient's age and gender, as predicting factors. The model achieved an accuracy of 91.3% in identifying cognitive dysfunction in PD patients, and plasma EV tau and Aβ1-42 are the most valuable factors. In conclusion, plasma EV tau and Aβ1-42 are significant markers of cognitive function in PD patients. Combining with the plasma EV α-synuclein, age, and sex, plasma EV tau and Aβ1-42 can identify cognitive dysfunction in PD patients. This study corroborates the prognostic roles of plasma EV tau and Aβ1-42 in PD.

中文翻译：

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血浆细胞外囊泡 tau 和 β-淀粉样蛋白作为帕金森病认知功能障碍的生物标志物

循环 tau 和 β-淀粉样蛋白在帕金森病 (PD) 中的作用，尤其是认知功能，仍然没有定论。细胞外囊泡 (EV) 在这些蛋白质直接从包括神经元在内的许多细胞中分泌后，将这些蛋白质运送到整个血液中。本研究旨在通过调查轻度至中度 PD 受试者（n  = 116）和非 PD 对照（n = 46）。分离血浆 EV，并使用基于免疫磁性还原的免疫测定来评估 EV 中 α-突触核蛋白、tau 和 β-淀粉样蛋白 1-42 (Aβ1-42) 的水平。然后应用人工神经网络 (ANN) 模型来预测认知功能障碍。我们观察到 PD 患者和对照之间的血浆 EV tau 和 Aβ1-42 没有显着差异。血浆 EV tau 与认知功能显着相关。此外，与具有最佳认知的 PD 患者相比，具有认知障碍的 PD 患者的血浆 EV tau 和 Aβ1-42 显着升高。ANN 模型使用血浆 EV α-突触核蛋白、tau 和 Aβ1-42，以及患者的年龄和性别作为预测因素。该模型在识别 PD 患者的认知功能障碍方面达到了 91.3% 的准确率，和血浆 EV tau 和 Aβ1-42 是最有价值的因素。总之，血浆 EV tau 和 Aβ1-42 是 PD 患者认知功能的重要标志物。结合血浆 EV α-突触核蛋白、年龄和性别，血浆 EV tau 和 Aβ1-42 可以识别 PD 患者的认知功能障碍。该研究证实了血浆 EV tau 和 Aβ1-42 在 PD 中的预后作用。