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Sökning: WFRF:(Wuolikainen Anna) > (2020-2024) > Biomarkers for diag...

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FältnamnIndikatorerMetadata
00005230nam a2200493 4500
001oai:DiVA.org:umu-222636
003SwePub
008240325s2024 | |||||||||||000 ||eng|
020 a 9789180703123q print
020 a 9789180703130q electronic
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-2226362 URI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a vet2 swepub-contenttype
072 7a dok2 swepub-publicationtype
1001 a Behzadi, Arvin,d 1994-u Umeå universitet,Neurovetenskaper4 aut0 (Swepub:umu)arbe0035
2451 0a Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis
264 1a Umeå :b Umeå University,c 2024
300 a 91 s.
338 a electronic2 rdacarrier
4900 a Umeå University medical dissertations,x 0346-6612 ;v 2290
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
653 a amyotrophic lateral sclerosis
653 a biomarkers
653 a neurofilaments
653 a cytokines
653 a troponin
653 a cystatin C
653 a Neurology
653 a neurologi
7001 a Forsberg, Karin,c Medicine doktor (Doctor of Philosophy)u Umeå universitet,Neurovetenskaper4 ths0 (Swepub:umu)nonkin02
7001 a Tjust, Anton E.,c Medicine doktor (Doctor of Philosophy),d 1988-u Umeå universitet,Neurovetenskaper4 ths0 (Swepub:umu)antj0003
7001 a Wuolikainen, Anna,c Medicine doktor (Doctor of Philosophy)u Umeå universitet,Kemiska institutionen4 ths0 (Swepub:umu)anawun00
7001 a Zetterström, Per,c Medicine doktor (Doctor of Philosophy)u Umeå universitet,Klinisk kemi4 ths0 (Swepub:umu)perzem02
7001 a Koskinen, Lars-Owe D.,c Professor,d 1955-u Umeå universitet,Neurovetenskaper4 ths0 (Swepub:umu)lako0002
7001 a Puschmann, Andreas,c Docent (Associate professor)u Institutionen för kliniska vetenskaper, Lunds universitet, Sverige4 opn
7102 a Umeå universitetb Neurovetenskaper4 org
8564 u https://umu.diva-portal.org/smash/get/diva2:1846645/FULLTEXT01.pdfx primaryx Raw objecty fulltext
8564 u https://umu.diva-portal.org/smash/get/diva2:1846645/SPIKBLAD01.pdfy spikblad
8564 u https://umu.diva-portal.org/smash/get/diva2:1846645/PREVIEW01.jpgx Previewy preview image
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222636

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