- Goldman, Jennifer G;
- Andrews, Howard;
- Amara, Amy;
- Naito, Anna;
- Alcalay, Roy N;
- Shaw, Leslie M;
- Taylor, Peggy;
- Xie, Tao;
- Tuite, Paul;
- Henchcliffe, Claire;
- Hogarth, Penelope;
- Frank, Samuel;
- Saint‐Hilaire, Marie‐Helene;
- Frasier, Mark;
- Arnedo, Vanessa;
- Reimer, Alyssa N;
- Sutherland, Margaret;
- Swanson‐Fischer, Christine;
- Gwinn, Katrina;
- Discovery, The Fox Investigation of New Biomarker;
- Kang, Un Jung
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.