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  • Dorst, JohannesDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)

Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • Elsevier,2023
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-206371
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-206371URI
  • https://doi.org/10.1016/j.ebiom.2023.104521DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Background: The emergence of potentially effective new therapies for genetic forms of amyotrophic lateral sclerosis (ALS) necessitates the identification of biomarkers to facilitate early treatment, prior to the onset of motor symptoms. Here, we sought to investigate whether metabolic alterations are detectable in presymptomatic ALS gene mutation carriers, and whether such alterations precede neurofilament light chain (NfL) changes in serum.Methods: Between 02/2014 and 11/2021, we prospectively studied 60 presymptomatic ALS gene mutation carriers (40% male, age 48.7 ± 14.9; 28 C9orf72, 22 SOD1, 10 other) compared to 73 individuals from the same families (47% male, age 47.4 ± 12.9) without pathogenic mutations as controls. Bioimpedance analysis (BIA) and indirect calorimetry were performed, and Body Mass Index (BMI), Fat Mass (FM), Body Fat Percentage, Body Water (BW), Lean Body Mass (LBM), Extracellular Mass (ECM), Body Cell Mass (BCM), ECM/BCM ratio, Cells Percentage, Phase Angle, Resting Metabolic Rate (RMR), Metabolic Ratio (MR), and NfL were measured. Participants and evaluators were blinded regarding gene carrier status.Findings: Presymptomatic ALS gene carriers showed reduced LBM (p = 0.02), BCM (p = 0.004), Cells Percentage (p = 0.04), BW (p = 0.02), Phase Angle (p = 0.04), and increased ECM/BCM ratio (p = 0.04), consistently indicating a loss of metabolically active body cells. While in C9orf72 mutation carriers all tissue masses were reduced, only metabolically active tissue was affected in SOD1 mutation carriers. Unexpectedly, RMR (p = 0.009) and MR (p = 0.01) were lower in presymptomatic ALS gene carriers compared to non-carriers. NfL serum levels were similar in mutation carriers and non-carriers (p = 0.60).Interpretation: The observed metabolic phenomena might reflect reduced physical activity and/or preemptive, insufficient compensatory mechanisms to prepare for the later hypermetabolic state. As pre-symptomatic biomarkers we propose ECM/BCM ratio and Phase Angle for SOD1, and a 4-compartment affection in BIA for C9orf72 mutation carriers.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Weydt, PatrickDepartment of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany (författare)
  • Brenner, DavidDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Witzel, SimonDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Kandler, KatharinaDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Huss, AndréDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Herrmann, ChristineDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Wiesenfarth, MaximilianDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Knehr, AntjeDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Günther, KorneliaDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Müller, KathrinInstitute for Human Genetics, University of Ulm, Ulm, Germany (författare)
  • Weishaupt, Jochen H.Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany (författare)
  • Prudlo, JohannesDepartment of Neurology, Rostock University Medical Center, German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany (författare)
  • Forsberg, KarinUmeå universitet,Neurovetenskaper(Swepub:umu)nonkin02 (författare)
  • Andersen, Peter M.,1962-Umeå universitet,Neurovetenskaper(Swepub:umu)pean0001 (författare)
  • Rosenbohm, AngelaDepartment of Neurology, University of Ulm, Ulm, Germany (författare)
  • Schuster, JoachimDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Roselli, FrancescoDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Dupuis, LucInserm, Université de Strasbourg, Strasbourg, France (författare)
  • Mayer, BenjaminInstitute for Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany (författare)
  • Tumani, HayrettinDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Kassubek, JanDepartment of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Ludolph, Albert C.Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany (författare)
  • Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, GermanyDepartment of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:EBioMedicine: Elsevier902352-3964

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