Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson's disease Features

Abstract

Objective: Examine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms. Background: CSF alpha‐synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha‐synuclein differentiate these groups is controversial. Correlations of alpha‐synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta‐amyloid, tau [total, phosphorylated]) are not fully understood. The relationships of these biomarkers with PD clinical features remain unclear. Methods: BioFIND, a cross‐sectional, observational study, examines clinical and biomarker characteristics in moderate‐advanced PD and matched healthy controls. We compared alpha‐synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and MDS‐UPDRS, motor phenotype, MoCA, and rapid eye movement sleep behavior disorder questionnaire scores in PD were examined. Results: CSF alpha‐synuclein was lower in PD versus controls (P = .01), controlling for age, gender, and education. Plasma and saliva alpha‐synuclein did not differ between PD and controls, and alpha‐synuclein did not significantly correlate among biofluids. CSF beta‐amyloid1‐42 was lower in PD versus controls (P < .01), and correlated weakly with MoCA recall scores (r = 0.23, P = .02). CSF alpha‐synuclein was lower in the postural instability/gait difficulty phenotype than other motor phenotypes (P < .01). No CSF biomarkers predicted or correlated with total motor or rapid eye movement sleep behavior disorder scores. CSF alpha‐synuclein correlated with beta‐amyloid1‐42, total‐tau, and phosphorylated‐tau (r = 0.41, 0.81, 0.43, respectively; Ps < .001). Conclusion: Lower CSF alpha‐synuclein is associated with diagnosis and motor phenotype in moderate‐advanced PD. Plasma and saliva alpha‐synuclein neither correlate with CSF alpha‐synuclein, nor distinguish PD from controls. CSF beta‐amyloid1‐42 remains a potential biomarker for cognitive impairment in PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Comparative study of cerebrospinal fluid α‐synuclein seeding aggregation assays for diagnosis of Parkinson's disease

“…[13][14][15] This is contrasted by the consistent finding that total α-synuclein protein levels are lower in CSF from PD patients compared to HCs at the population level, with significant overlap between the two groups. 17,28,29 Although the concordance rate was high between the two assays (92%; Fig. 1), we did not find any systematic explanation for the discrepant findings.…”

“…Therefore, we undertook a blinded study of two similar assays that were separately developed by independent laboratories. These two platforms tested CSF from the same subjects in the BioFIND cohort, which utilized standardized biospecimen collection protocols of clinically typical and well‐defined moderate PD patients and healthy controls …”

“…These two platforms tested CSF from the same subjects in the BioFIND cohort, which utilized standardized biospecimen collection protocols of clinically typical and well-defined moderate PD patients and healthy controls. 17,18…”

Parkinson’s disease biomarkers based on α‐synuclein

“…An initial study reported increased a-syn levels in plasma of PD patients compared with healthy controls (Lee et al 2006). However, subsequent reports found levels of total a-syn to be either increased (Duran et al 2010;Lin et al 2017), decreased (Li et al 2007), or not significantly different Foulds et al 2011;Mollenhauer et al 2011;Park et al 2011;Goldman et al 2018). Despite extensive efforts, results as to whether total a-syn concentrations in the blood differ between PD patients and healthy subjects yielded inconsistent findings.…”

CSF Biomarkers for Early Diagnosis of Synucleinopathies: Focus on Idiopathic RBD

“…They identified greater increase of CSF αsynuclein levels after 1-year follow-up in patients with RBD compared to those without RBD. Meanwhile, in the Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease (BioFIND), a cross-sectional and observational study assessing clinical features and CSF biomarkers of 115 moderate and advanced PD, CSF αsynuclein levels did not correlate with RBD questionnaire total score [49].…”