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. 2015 Jan 6;84(1):57-63.
doi: 10.1212/WNL.0000000000001098. Epub 2014 Nov 19.

CSF biomarkers and clinical progression of Parkinson disease

Affiliations

CSF biomarkers and clinical progression of Parkinson disease

Sara Hall et al. Neurology. .

Abstract

Objective: To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease (PD).

Methods: Patients and controls were recruited from hospitals in southern Sweden as part of the prospective and longitudinal Swedish BioFinder Study. In the present study, we included 42 patients with PD and 69 controls who had clinical assessment and lumbar puncture at baseline. Baseline CSF samples were analyzed for α-synuclein (αSyn), β-amyloid 1-42 (Aβ42), tau, phosphorylated tau, and neurofilament light. Associations between CSF markers at baseline and change in clinical characteristics after 2 years of follow-up were investigated using multivariate models adjusting for age, sex, disease duration, and levodopa-equivalent daily dose.

Results: Higher levels of αSyn within the PD group were associated with progression of motor symptoms and cognitive decline over 2 years, indicated by significant relationships between αSyn and change in Hoehn and Yahr (β = 0.394, p = 0.043), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (β = 0.449, p = 0.013), Timed Up and Go (β = 0.406, p = 0.023), and A Quick Test of Cognitive Speed (β = 0.423, p = 0.018). Lower levels of Aβ42 were associated with worsening of performance on delayed memory recall (F = 5.834, p = 0.022). Finally, high levels of phosphorylated tau were associated with worsening in motor symptoms (UPDRS-III, β = 0.350, p = 0.045; Hoehn and Yahr, β = 0.366, p = 0.038).

Conclusion: We found evidence of a link between higher levels of αSyn at baseline and worsening of motor symptoms and cognitive speed over 2 years in PD. Increased αSyn might be a marker of more intense synaptic degeneration in PD. The results indicate that cortical amyloid pathology (low CSF Aβ42) is associated with memory decline.

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Figures

Figure 1
Figure 1. Correlations of CSF levels of αSyn with tau, p-tau, and NFL
Correlations of CSF levels of αSyn with tau (A), p-tau (B), and NFL (C) in the Parkinson disease group. Black line indicates a linear regression, blue lines 95% confidence intervals. αSyn = α-synuclein; NFL = neurofilament light; p-tau = phosphorylated tau.
Figure 2
Figure 2. CSF Aβ42 and worsening on ADAS-cog item 3 over 2 years
Boxplot showing change in number of correct answers on ADAS-cog item 3 over 2 years in Aβ42 >550 ng/L compared with Aβ42 <550 ng/L in PD patients. Aβ42 = β-amyloid 1–42; ADAS-cog = Alzheimer's Disease Assessment Scale–cognitive.
Figure 3
Figure 3. Correlations of CSF αSyn with change in AQT and UPDRS-III, and CSF p-tau with UPDRS-III change
Correlations of (A) αSyn with worsening in AQT over 2 years (change in AQT is normalized using Blom's method), (B) αSyn with worsening in UPDRS-III over 2 years, and (C) p-tau with increase in UPDRS-III over 2 years in patients with Parkinson disease. αSyn and p-tau are log-transformed. Black line indicates a linear regression, blue lines 95% confidence intervals. αSyn = α-synuclein; AQT = A Quick Test of Cognitive Speed; p-tau = phosphorylated tau; UPDRS-III = Unified Parkinson's Disease Rating Scale, Part III.

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