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Neurofilaments as biomarkers of neuronal damage

Doktorsavhandling
Författare Fani Pujol-Calderón
Datum för examination 2019-10-18
ISBN 978-91-7833-551-0
Förlag Göteborgs universitet
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Språk en
Länkar hdl.handle.net/2077/60776
Ämnesord neurofilaments, biomarker, neurodegenerative disease, stroke
Ämneskategorier Neurovetenskaper

Sammanfattning

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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