The value of cerebrospinal fluid alpha-synuclein and the tau/alpha-synuclein ratio for diagnosis of neurodegenerative disorders with Lewy pathology

Abstract

Background and purpose Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are three of the most common neurodegenerative disorders. Up to 20% of these patients have the wrong diagnosis, due to overlapping symptoms and shared pathologies. A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking. Using well‐defined, community‐based cohorts and validated analytical methods, the diagnostic value of CSF total‐α‐synuclein (t‐α‐syn) alone and in combination with total tau (t‐tau) in newly diagnosed patients with PD, DLB and AD was determined. Methods Cerebrospinal fluid concentrations of t‐α‐syn were assessed using our validated in‐house enzyme‐linked immunosorbent assay in 78 PD patients, 20 AD patients, 19 DLB patients and 32 controls. t‐tau was measured using a commercial assay. Diagnostic performance was assessed by receiver operating characteristic curve analysis. Results Compared to controls (mean 517 pg/ml), significantly lower levels of CSF t‐α‐syn in patients with PD (434 pg/ml, 16% reduction, P = 0.036), DLB (398 pg/ml, 23% reduction, P = 0.009) and AD (383 pg/ml, 26% reduction, P = 0.014) were found. t‐α‐syn levels did not differ significantly between PD, DLB and AD. The t‐tau/t‐α‐syn ratio showed an improved performance compared to the single markers. Conclusion This is the first study to compare patients with PD, DLB and AD at the time of diagnosis. It was found that t‐α‐syn can contribute as a teammate with tau in a CSF biomarker panel for PD and DLB, and strengthen the existing biomarker panel for AD.