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Cerebrospinal Fluid Galectin-1 Levels Discriminate Patients with Parkinsonism from Controls.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder in elderly people. Currently, the diagnosis of PD is based on neurological examination, neuroimaging, and the response to dopaminergic medication. The diagnosis can be challenging, especially at early disease stages, when the symptoms of patients with atypical parkinsonism (APD) may strongly overlap. Therefore, reliable biomarkers that are able to identify patients with PD are much needed. Here, we aimed to identify and validate new biomarkers for PD in cerebrospinal fluid (CSF). We performed a profiling experiment using mass spectrometry (MS) of CSF from ten PD patients and ten matched non-neurological controls. We selected one protein, galectin-1 (Gal-1), which was differentially expressed in PD vs. controls, and quantified its concentrations in CSF by enzyme-linked immunosorbent assay (ELISA) in three new cohorts of 37 PD patients, 21 APD patients, and 44 controls. CSF levels of Gal-1 were lower in PD in both the discovery and validation experiments and discriminated PD from controls with moderate-high accuracy levels (ELISA: area under the curve?=?0.7). Similar levels of Gal-1 were found in PD and APD. Gal-1 levels were correlated to age in all groups and correlated in the PD patients to CSF levels of total tau, phosphorylated tau, neurofilament light chain (NFL), and the mini-mental state examination (MMSE) score. We conclude that MS profiling of proteins may be a useful tool to identify novel biomarkers of neurological diseases and that CSF Gal-1 levels may discriminate PD from non-neurological controls.

SUBMITTER: Marques TM

PROVIDER: S-EPMC6647396 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Cerebrospinal Fluid Galectin-1 Levels Discriminate Patients with Parkinsonism from Controls.

Marques Tainá M TM van Rumund Anouke A Bruinsma Ilona B IB Wessels Hans J C T HJCT Gloerich Jolein J Esselink Rianne A J RAJ Bloem Bastiaan R BR Kuiperij H Bea HB Verbeek Marcel M MM

Molecular neurobiology 20181121 7

Parkinson's disease (PD) is the second most common neurodegenerative disorder in elderly people. Currently, the diagnosis of PD is based on neurological examination, neuroimaging, and the response to dopaminergic medication. The diagnosis can be challenging, especially at early disease stages, when the symptoms of patients with atypical parkinsonism (APD) may strongly overlap. Therefore, reliable biomarkers that are able to identify patients with PD are much needed. Here, we aimed to identify an ...[more]

PMID: 30465235

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Project description:Rapid determination of an infective aetiology causing neurological inflammation in the cerebrospinal fluid can be challenging in clinical practice. Post-surgical nosocomial infection is difficult to diagnose accurately, as it occurs on a background of altered cerebrospinal fluid composition due to the underlying pathologies and surgical procedures involved. There is additional diagnostic difficulty after external ventricular drain or ventriculoperitoneal shunt surgery, as infection is often caused by pathogens growing as biofilms, which may fail to elicit a significant inflammatory response and are challenging to identify by microbiological culture. Despite much research effort, a single sensitive and specific cerebrospinal fluid biomarker has yet to be defined which reliably distinguishes infective from non-infective inflammation. As a result, many patients with suspected infection are treated empirically with broad-spectrum antibiotics in the absence of definitive diagnostic criteria. To begin to address these issues, we examined cerebrospinal fluid taken at the point of clinical equipoise to diagnose cerebrospinal fluid infection in 14 consecutive neurosurgical patients showing signs of inflammatory complications. Using the guidelines of the Infectious Diseases Society of America, six cases were subsequently characterized as infected and eight as sterile inflammation. Twenty-four contemporaneous patients with idiopathic intracranial hypertension or normal pressure hydrocephalus were included as non-inflamed controls. We measured 182 immune and neurological biomarkers in each sample and used pathway analysis to elucidate the biological underpinnings of any biomarker changes. Increased levels of the inflammatory cytokine interleukin-6 and interleukin-6-related mediators such as oncostatin M were excellent indicators of inflammation. However, interleukin-6 levels alone could not distinguish between bacterially infected and uninfected patients. Within the patient cohort with neurological inflammation, a pattern of raised interleukin-17, interleukin-12p40/p70 and interleukin-23 levels delineated nosocomial bacteriological infection from background neuroinflammation. Pathway analysis showed that the observed immune signatures could be explained through a common generic inflammatory response marked by interleukin-6 in both nosocomial and non-infectious inflammation, overlaid with a toll-like receptor-associated and bacterial peptidoglycan-triggered interleukin-17 pathway response that occurred exclusively during infection. This is the first demonstration of a pathway dependent cerebrospinal fluid biomarker differentiation distinguishing nosocomial infection from background neuroinflammation. It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort.

Dataset Information

Cerebrospinal Fluid Galectin-1 Levels Discriminate Patients with Parkinsonism from Controls.

Publications

Cerebrospinal Fluid Galectin-1 Levels Discriminate Patients with Parkinsonism from Controls.

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