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Neurofilaments as biomarkers of neuronal damage

Doctoral thesis
Authors Fani Pujol-Calderón
Date of public defense 2019-10-18
ISBN 978-91-7833-551-0
Publisher Göteborgs universitet
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Keywords neurofilaments, biomarker, neurodegenerative disease, stroke
Subject categories Neurosciences


Different neurodegenerative diseases have overlapping symptomatology and pathology and have thus become a challenge to modern medicine to achieve a correct diagnosis. The aim of the thesis was to evaluate the use of neurofilaments as biomarkers of neuronal damage by testing their ability to discriminate between different neurodegenerative diseases as well as assessing whether higher neurofilments predict a poorer clinical outcome in ischemic stroke. For these purposes, we developed two new Enzyme-Linked ImmunoSorbent Assays (ELISAs) for the quantification of neurofilament light (NFL) and phosphorylated neurofilament heavy (pNFH) in cerebrospinal fluid (CSF). The new NFL and pNFH ELISAs presented good analytical performance and both NFL and pNFH concentrations were valid across different analytical approaches. CSF-NFL concentrations were significantly higher in inflammatory demyelinating diseases and Alzheimer’s disease when compared to Parkinson’s disease or controls. In ischemic stroke, both CSF and blood NFL and pNFH reflected the temporal dynamics of post ischemic damage of axons. Finally, both CSF-NFL and CSF-pNFH were increased in amyotrophic lateral sclerosis (ALS) compared to other neurological conditions mimicking ALS and controls. Both NFL and pNFH proved to be sensitive and reliable biomarkers of neuronal damage. These findings support the use of neurofilaments as disease intensity markers and suggest that both NFL and pNFH can be useful laboratory tests in the diagnostic work-up of patients with suspected neurodegenerative diseases.

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