Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis

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MARC

Behzadi, Arvin,1994-Umeå universitet,Neurovetenskaper (author)

Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis

BookEnglish2024

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Umeå :Umeå University,2024
91 s.
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-222636
ISBN:9789180703123
ISBN:9789180703130
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222636URI

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Language:English
Summary in:English

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Subject category:vet swepub-contenttype
Subject category:dok swepub-publicationtype

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Umeå University medical dissertations,0346-6612 ;2290

Notes

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of upper and lower motor neurons, leading to paresis, muscle atrophy, and respiratory failure. ALS can be difficult to diagnose and prognosticate early.Aim: To investigate the diagnostic and prognostic characteristics of biomarkers in cerebrospinal fluid (CSF), plasma, and skeletal muscle tissue in patients with ALS.Paper I: Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) were analyzed in CSF using enzyme-linked immunosorbent assay (ELISA), and NFL in plasma was analyzed using single-molecule array (SIMOA). CSF NFL, CSF pNFH, and plasma NFL concentrations can differentiate ALS patients from ALS mimics, and were significantly negatively correlated with the disease duration in ALS patients.Paper II: Myosin heavy chain (MyHC) isoforms in extraocular muscles were investigated using immunofluorescence. Control donors had significantly higher proportion of myofibers containing MyHCIIa and significantly lower proportion of myofibers containing MyHCeom in the global layer compared to spinal-onset ALS and bulbar-onset ALS donors. Disease duration in the spinal-onset ALS donors was significantly correlated with the proportion of myofibers containing MyHCIIa in the global layer and MyHCeom in the orbital layer.Paper III: The study combined the neurofilament concentrations from Paper I, with cytokines previously analyzed in CSF and plasma using SIMOA, to investigate distinct molecular phenotypes in ALS. Patients with bulbar-onset ALS had significantly higher concentrations of CSF tumor necrosis factor α (TNF-α) compared to ALS mimics. TNF-α and NFL were significantly correlated with each other in both CSF and plasma in ALS patients. Combined analysis of NFL and IL-6 in plasma identified molecular prognostic subgroups in ALS patients.Paper IV: Creatine kinase (CK), high-sensitivity cardiac troponin T (hs-cTnT), hs-cTnI, and cystatin C (CysC) were analyzed in plasma in a fully accredited laboratory. CK and hs-cTnT concentrations were significantly elevated in limb-onset ALS compared to controls and bulbar-onset ALS. hs-cTnT concentrations were significantly elevated in truncal-onset ALS compared to controls and bulbar-onset ALS. Multivariable Cox proportional hazards models indicated elevated concentrations of CysC as a significant marker for worse prognosis in ALS.Conclusions: The papers report diagnostic and prognostic characteristics of biomarkers in CSF, plasma, and muscle tissue in ALS patients. The significant findings for biomarkers in plasma could be of value since plasma sampling does not involve a lumbar puncture.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
amyotrophic lateral sclerosis
biomarkers
neurofilaments
cytokines
troponin
cystatin C
Neurology
neurologi

Added entries (persons, corporate bodies, meetings, titles ...)

Forsberg, Karin,Medicine doktor (Doctor of Philosophy)Umeå universitet,Neurovetenskaper(Swepub:umu)nonkin02 (thesis advisor)
Tjust, Anton E.,Medicine doktor (Doctor of Philosophy),1988-Umeå universitet,Neurovetenskaper(Swepub:umu)antj0003 (thesis advisor)
Wuolikainen, Anna,Medicine doktor (Doctor of Philosophy)Umeå universitet,Kemiska institutionen(Swepub:umu)anawun00 (thesis advisor)
Zetterström, Per,Medicine doktor (Doctor of Philosophy)Umeå universitet,Klinisk kemi(Swepub:umu)perzem02 (thesis advisor)
Koskinen, Lars-Owe D.,Professor,1955-Umeå universitet,Neurovetenskaper(Swepub:umu)lako0002 (thesis advisor)
Puschmann, Andreas,Docent (Associate professor)Institutionen för kliniska vetenskaper, Lunds universitet, Sverige (opponent)
Umeå universitetNeurovetenskaper (creator_code:org_t)

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