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J Neurol Neurosurg Psychiatry. 2019 Mar 13. pii: jnnp-2018-320151. doi: 10.1136/jnnp-2018-320151. [Epub ahead of print]

Proximity extension assay testing reveals novel diagnostic biomarkers of atypical parkinsonian syndromes.

Author information

1
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK e.jabbari@ucl.ac.uk.
2
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
3
Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, UK.
4
Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, University College London, London, UK.
5
Department of Neurology, Royal Gwent Hospital, Newport, UK.
6
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
7
Department of Clinical Neurosciences and MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
8
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
9
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

OBJECTIVE:

The high degree of clinical overlap between atypical parkinsonian syndromes (APS) and Parkinson's disease (PD) makes diagnosis challenging. We aimed to identify novel diagnostic protein biomarkers of APS using multiplex proximity extension assay (PEA) testing.

METHODS:

Cerebrospinal fluid (CSF) samples from two independent cohorts, each consisting of APS and PD cases, and controls, were analysed for neurofilament light chain (NF-L) and Olink Neurology and Inflammation PEA biomarker panels. Whole-cohort comparisons of biomarker concentrations were made between APS (n=114), PD (n=37) and control (n=34) groups using logistic regression analyses that included gender, age and disease duration as covariates.

RESULTS:

APS versus controls analyses revealed 11 CSF markers with significantly different levels in cases and controls (p<0.002). Four of these markers also reached significance (p<0.05) in APS versus PD analyses. Disease-specific analyses revealed lower group levels of FGF-5, FGF-19 and SPOCK1 in multiple system atrophy compared with progressive supranuclear palsy and corticobasal syndrome. Receiver operating characteristic curve analyses suggested that the diagnostic accuracy of NF-L was superior to the significant PEA biomarkers in distinguishing APS, PD and controls. The biological processes regulated by the significant proteins include cell differentiation and immune cell migration. Delta and notch-like epidermal growth factor-related receptor (DNER) had the strongest effect size in APS versus controls and APS versus PD analyses. DNER is highly expressed in substantia nigra and is an activator of the NOTCH1 pathway which has been implicated in the aetiology of other neurodegenerative disorders including Alzheimer's disease.

CONCLUSIONS:

PEA testing has identified potential novel diagnostic biomarkers of APS.

KEYWORDS:

cerebrospinal fluid; corticobasal degeneration; diagnostic test assessment; multiple system atrophy; progressive supranuclear palsy

PMID:
30867224
DOI:
10.1136/jnnp-2018-320151
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Conflict of interest statement

Competing interests: None declared.

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