Objective: To identify the biomarker associated with progressive supranuclear palsy (PSP) for better understanding of a pathophysiology and clinical diagnosis.

Background: PSP is one of the neurodegenerative diseases characterized by 4-repeat tau pathology. The typical PSP presents with parkinsonism, vertical supranuclear gaze palsy and postural instability with falls. Recently, various clinical subtypes of PSP have been reported, it is sometimes difficult to diagnose in the early phase of PSP.

Method: Cerebrospinal fluid (CSF) samples from 8 PSP patients (mean age; 72.6 ys) and from 8 healthy control (CTL) individuals (72.1 ys) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) method as a discovery study to identify a biomarker for PSP. CFS samples from a different cohort of 6 PSP patients (74.5 ys), 6 Parkinson’s disease (PD) patients (74.5 ys) and 6 CTL (74.3 ys) were used in the second study. The candidate protein by discovery study was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. In the validation study, CFS samples from a different cohort of 53 PSP patients (73.6 ys), 24 PD patients (73.0 ys), 15 corticobasal syndrome (CBS) patients (73.5 ys) and 20 CTL (69.2 ys) were analyzed by enzyme-linked immunosorbent assay (ELISA).

Results: The candidate protein (m/z 6255) specific to PSP was identified as the partial fragment of chromogranin B (CHGB). The mean CHGB levels in CSF were 76.8 μg/mL in PSP patients, 61.5 μg/mL in PD patients, 61.2 μg/mL in CBS patients and 59.0 μg/mL in CTL subjects. CHGB levels in PSP patients were significantly higher than it in PD patients, CBS patients and CTL subjects (p < 0.05). Receiver operating characteristics (ROC) area under the curve (AUC) analysis of a multivariate logistic model of CHGB revealed a ROC AUC of 0.671, a sensitivity of 62.3% and a specificity of 66.1%.

Conclusion: The result of the SELDI-TOF MS profiling indicated that CHGB in CSF had a high diagnostic potential for PSP.　CHGB is an acidic soluble molecule widely distributed in nerve cells and one of the neurosecretory proteins. The association with central nervous system diseases has been reported, and it is expected to be a potential research candidate molecule for elucidating the pathogenesis of PSP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/chromogranin-b-in-cerebrospinal-fluid-as-a-novel-biomarker-for-progressive-supranuclear-palsy/