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 Aß42, tau [total τΤ and phosphorylated τp-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 Aß42, τΤ and τp-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 Aß42 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 Aß42 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.

Plasma alpha-synuclein levels in patients with Parkinson's disease: a systematic review and meta-analysis.

OBJECTIVE: To date, there are no definitive biomarkers for diagnose Parkinson's disease (PD). The detection of α-synuclein (α-Syn) in plasma of PD patients has yielded promising but inconclusive results. To determine the performance of α-Syn as a diagnostic biomarker of PD, we used a meta-analysis. METHODS: We identified 173 studies through a systematic literature review. From those, only studies reporting data on total α-Syn levels were included in the meta-analysis (10 publications, 1302 participants). Quality of studies was assessed by Newcastle-Ottawa scale. RESULTS: The α-Syn levels were significantly higher in PD patients than healthy controls (standardized mean difference [SMD] = 0.778, 95% confidence interval = 0.284 to 1.272, p = 0.002). Similar results were found after omitting any individual study from meta-analysis, with SMD ranges from 0.318 (95% CI = 0.064 to 0.572, p = 0.014) to 0.914 (95% CI = 0.349 to 1.480, p = 0.002). According to meta-regression analysis, increased mean patients age (slope = - 0.232, 95% CI = - 0.456 to - 0.008, p = 0.042), increased total number of participants (slope = - 0.007, 95% CI = - 0.013 to - 0.0004, p = 0.038), and increased percentage of males (slope = - 6.444, 95% CI = - 10.841 to - 2.047, p = 0.004) were associated with decreased SMD of α-Syn levels across studies. We did not find any significant association between the SMD in α-Syn levels and disease duration, disease severity, and quality of studies. Most of studies applied ELISA assays. CONCLUSION: Total plasma α-Syn levels were higher in PD patients than controls. Analytical factors were important limitations.

Neuropsychiatric symptoms and α-Synuclein profile of patients with Parkinson's disease dementia, dementia with Lewy bodies and Alzheimer's disease.

INTRODUCTION: Given the overlapping of neuropathological, neurochemical and neuropsychiatric profiles of Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), their differential diagnosis is challenging. Specific neuropsychiatric features or biomarkers, such as cerebrospinal fluid (CSF) α-Synuclein (α-Syn), may aid in differential diagnosis. This study aims to compare the neuropsychiatric and CSF α-Syn profiles in these conditions, and to investigate the possible association between CSF α-Syn levels and neuropsychiatric symptoms. METHODS: We conducted a prospective cross-sectional study, between January 2013 and January 2015, with 16 PDD, 28 DLB and 19 AD patients. All participants underwent a detailed clinical, neuropsychological, neuropsychiatric [Neuropsychiatric Inventory (NPI)] and CSF α-Syn analysis. RESULTS: Significantly greater NPI Hallucinations Subitem score was found in the PDD and DLB groups compared to AD (both p < 0.001). NPI Agitation score was greater in the DLB compared to PDD group (p = 0.012). NPI Sleep score was greater in the DLB compared to AD group (p = 0.001). Total NPI score was greater in the DLB compared to AD and PDD groups. To discriminate between the DLB and AD and between DLB and PDD groups, logistic regression analysis showed that both NPI scores and α-Syn levels were independently associated. There was no correlation between NPI scores and α-Syn levels. Increased NPI scores and α-Syn levels are associated with greater likelihood for being in DLB than in PDD or AD groups. ROC analysis showed that the combination of NPI and α-Syn increases the discriminative ability of each marker alone (p < 0.001) with AUC equal to 0.95 (95% CI 0.91-0.99). CONCLUSION: NPI scores and CSF α-Syn levels were useful as independent variables to differentiate DLB from PDD and AD.