Objective: Evaluate associations between CSF biomarkers of neurodegeneration and clinical phenotype in Parkinson’s disease (PD) participants of the BioFIND cohort. 

Background: Levels of CSF α-synuclein are lower in PD compared to healthy controls (HC) and lower levels of CSF beta-amyloid 1-42 (AB1-42) have been demonstrated to predict cognitive decline in PD. However, the relationship between CSF biomarkers and PD motor phenotype or non-motor symptoms is not well understood in moderate to advanced PD. 

Methods: BioFIND is a cross-sectional, observational, case control study examining a cohort of moderate to advanced PD and matched HC participants. Clinical measures including MDS-UPDRS, Montreal Cognitive Assessment (MoCA), and REM Sleep Behavior Disorder (RBD) Questionnaire were assessed for correlations with CSF α-synuclein, AB1-42, total tau (t-tau), and phosphorylated tau (p-tau) in PD participants. We also assessed the relationship between these CSF biomarkers and PD motor phenotype (tremor dominant (TD) versus postural instability/gait disorder (PIGD). 

Results: Mean CSF α-synuclein (1462.22 versus 1706.44 pg/ml, p=.012) and AB1-42 (297.62 versus 333.40, p=0.004) were lower in PD versus controls. None of the CSF biomarkers correlated with, or predicted MDS-UPDRS total or motor scores. However, CSF levels of α-synuclein were lower among PIGD participants (1210.2±485.7 pg/ml) (mean±SD) compared to those with TD phenotype (1590.6±690.4 pg/ml) (unequal variance t-test: -3.05, p=0.003). The only CSF biomarker associated with cognition was AB1-42, which was non-parametrically correlated with the remote recall subscore of the MoCA (Spearman’s rho =0.215, p=0.025). There were no significant correlations between CSF biomarkers and dichotomized RBD scores in this cohort. CSF α-synuclein was most strongly correlated with t-tau (r=0.806) and modestly with p-tau (r=0.434) and AB1-42 (r=0.402) (p’s < 0.0005).

Conclusions: Lower CSF α-synuclein is associated with PIGD motor phenotype in moderate to advanced PD participants in the BioFIND cohort, thereby extending this relationship from early to more advanced PD. CSF AB1-42, α-synuclein, t-tau, and p-tau levels do not correlate with RBD. In contrast, CSF AB1-42 remains an important potential biomarker for cognitive impairment in PD. 

References: Kang UJ, Goldman JG, Alcalay RN, et al. The BioFIND study: characteristics of a clinically typical Parkinson’s disease biomarker cohort. Mov Disord 2016;31:924-932. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-csf-biomarkers-with-motor-and-non-motor-features-in-moderately-advanced-parkinsons-disease-cohort-the-biofind-study/