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

Abstract

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.

A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

“…EVs in this study were isolated using the exoEasy Maxi kit, and confirmed to be mainly exosomes by the presence of exosomal markers CD9, CD63 and TSG 101. The levels of tau and Aβ1-42 in the EVs were measured by immunomagnetic reduction assay [ 84 ].…”

Blood-based biomarker in Parkinson’s disease: potential for future applications in clinical research and practice

“…Aβ and tau have also been detected in exosomes/extracellular vesicles (EV). Although tau and Aß42 plasma EV levels did not differ between PD patients and controls, elevated levels of both proteins were significantly associated with cognitive impairment and combined with other parameters including aSyn in EV identified cognitively impaired PD patients with high accuracy (Chung et al 2021 ).…”

Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma

“…EVs and particularly exosomes have a large potential as non-invasive diagnostic biomarker carriers for neurodegenerative diseases and various studies reported them as being a source for biomarkers in Alzheimer’s disease (AD) [ 58 , 59 , 60 , 61 , 62 ], Parkinson’s disease (PD) [ 63 , 64 , 65 , 66 , 67 ], amyotrophic lateral sclerosis (ALS) [ 50 , 68 , 69 ], and prion disease [ 48 ]. The amyloid β (Aβ), tau, α-synuclein, and superoxide dismutase 1 were previously quantified in EVs in AD, PD, and ALS, and in several studies the correlation of their levels with the disease stages were found [ 51 , 60 , 64 , 70 , 71 , 72 , 73 , 74 ]. In HD, information about protein composition of EVs is missing [ 57 ] and the presence of HTT protein or its fragments in the EVs isolated from blood plasma have not yet been reported.…”