Plasma Levels of α-Synuclein, Aβ-40 and T-tau as Biomarkers to Predict Cognitive Impairment in Parkinson's Disease.

Objective In this study, we assessed plasma biomarkers to identify cognitive impairment in patients with Parkinson’s disease (PD) by using ultra-sensitive immunomagnetic reduction-based immunoassay (IMR). Methods The study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Participants received complete cognitive function assessments using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating. PD patients with an MMSE score of < 28 were defined as having cognitive impairment. Meanwhile, a 99mTc-TRODAT-1 scan was performed and plasma levels of Aβ-40, Aβ-42, T-tau, and α-synuclein were evaluated using IMR, subsequent correlation analyses were then performed. Results Compared with normal adults, PD patients have higher plasma levels of α-synuclein and T-tau, and a lower level of Aβ-40 (p<0.05). Plasma levels of α-synuclein (r = -0.323, p=0.002), Aβ-40 (r = 0.276, p=0.01), and T-tau (r = -0.322, p=0.002) are significantly correlated with MMSE scores. The TRODAT scan results, including visual inspection and quantification, revealed significant correlations between Aβ-40 and PD. Multiple regression analysis showed that the plasma levels of Aβ-40 (OR=0.874, 95% CI=0.796 - 0.959) and α-synuclein (OR=1.682, 95% CI=1.017 - 2.782) were independently associated with PD patients with cognitive impairment. The cutoff values for predicting cognitive deficits in PD patients were 45.101 pg/ml of Aβ-40, (Area under curve (AUR) = 0.791), and 0.389 pg/ml of α-synuclein, (AUR = 0.790). Conclusion Plasma levels of α-synuclein and Aβ-40 are potential biomarkers for the detection of cognitive impairment in PD patients.