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

Artikel i vetenskaplig tidskrift
Författare E. Jabbari
J. Woodside
T. Guo
N. K. Magdalinou
V. Chelban
D. Athauda
A. J. Lees
T. Foltynie
H. Houlden
A. Church
M. T. M. Hu
J. B. Rowe
Henrik Zetterberg
H. R. Morris
Publicerad i Journal of Neurology Neurosurgery and Psychiatry
Volym 90
Nummer/häfte 7
Sidor 768-773
ISSN 0022-3050
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 768-773
Språk en
Länkar dx.doi.org/10.1136/jnnp-2018-320151
Ämnesord progressive supranuclear palsy, disease, csf, Neurosciences & Neurology, Psychiatry, Surgery
Ämneskategorier Neurovetenskaper

Sammanfattning

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.

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