Plasma extracellular vesicles tau and β-amyloid as biomarkers of cognitive dysfunction of Parkinson's disease.

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.