Plasma alpha-synuclein and phosphorylated tau 181 as a diagnostic biomarker panel for de novo Parkinson's disease

The use of a diagnostic panel comprising multiple biomarkers has the potential to accurately diagnose Parkinson's disease (PD). However, a panel consisting solely of plasma biomarkers to diagnose PD is not available. This study aimed to examine the diagnostic ability of plasma biomarker panels for de novo PD using novel digital ultrasensitive immunoassay technology. We recruited 45 patients with de novo PD and 20 healthy controls (HCs). The concentrations of plasma alpha-synuclein (alpha-syn), amyloid beta-42 (A beta 42), A beta 40, phosphorylated tau 181 (p-tau181), neurofilament light (NFL), and glial fibrillary acidic protein (GFAP) were quantified using the ultrasensitive single molecule array (Simoa) platform. Patients with de novo PD had higher plasma levels of alpha-syn and p-tau181 than HCs, adjusting for age and sex. Plasma levels of alpha-syn and p-tau181 were positively correlated in de novo PD patients. Higher plasma alpha-syn levels were significantly associated with worse Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor scores, modified Hoehn and Yahr (H-Y) stages, and increased risk of PD with mild cognitive impairment (PD-MCI). Higher plasma p-tau181 concentrations were linked to worse H-Y stages. The diagnostic panel using plasma alpha-syn and p-tau181, combined with age and sex, showed good performance in discriminating de novo PD patients from HCs (area under the curve = 0.806). These findings suggest that plasma alpha-syn and p-tau181 together may be a promising diagnostic biomarker panel for de novo PD patients.