High discriminatory ability of peripheral and CFSF biomarkers in Lewy body diseases

Differential diagnosis between Parkinson's disease (PD) Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), namely spectrum of Lewy bodies disorders (LBDs), may be challenging, and their common underlying pathophysiology is debated. Our aim was to examine relationships among neurodegenerative biomarkers [alpha-synuclein (α-Syn), Alzheimer’s Disease (AD)—related (beta‐amyloid Aβ 42 , tau [total τ Τ and phosphorylated τ p−181 ]), dopaminergic imaging (DATSCAN–SPECT)] and spectrum of LBD. This is a cross‐sectional prospective study in 30 PD, 18 PDD, 29 DLB patients and 30 healthy controls. We compared α‐Syn in CSF, plasma and serum and CSF Aβ 42 , τ Τ and τ p−181 across these groups. Correlations between such biomarkers and motor, cognitive/neuropsychiatric tests, and striatal asymmetry indexes were examined. CSF α-Syn was higher in DLB versus PD/PDD/controls, and lower in PD and PDD patients compared to controls (all p < 0.001). Serum α-Syn levels were higher in all patient groups compared to controls. After excluding those DLB patients with CSF AD profile, plasma and serum Syn levels were higher in the LBD group as a whole compared to controls. The combination of CSF α-Syn, serum α-Syn and Aβ 42 for comparison between PD and DLB [AUC = 0.96 (95% CI 0.90–1.00)] was significantly better when compared to serum α-Syn alone ( p < 0.001). Correlation analyses of biomarkers with cognitive/neuropsychiatric scales revealed some associations, but no consistent, cohesive picture. Peripheral biomarkers such as serum α-Syn, and CSF α-Syn and Aβ 42 may contribute as potential biomarkers to separate LBDs from controls and to differentiate DLB from the other LBDs with high sensitivity and specificity among study groups.