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Metabolic alteratio...
Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers
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- Dorst, Johannes (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Weydt, Patrick (författare)
- Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
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- Brenner, David (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Witzel, Simon (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Kandler, Katharina (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Huss, André (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Herrmann, Christine (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Wiesenfarth, Maximilian (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Knehr, Antje (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Günther, Kornelia (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Müller, Kathrin (författare)
- Institute for Human Genetics, University of Ulm, Ulm, Germany
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- Weishaupt, Jochen H. (författare)
- Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany
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- Prudlo, Johannes (författare)
- Department of Neurology, Rostock University Medical Center, German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
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- Forsberg, Karin (författare)
- Umeå universitet,Neurovetenskaper
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- Andersen, Peter M., 1962- (författare)
- Umeå universitet,Neurovetenskaper
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- Rosenbohm, Angela (författare)
- Department of Neurology, University of Ulm, Ulm, Germany
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- Schuster, Joachim (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Roselli, Francesco (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Dupuis, Luc (författare)
- Inserm, Université de Strasbourg, Strasbourg, France
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- Mayer, Benjamin (författare)
- Institute for Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
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- Tumani, Hayrettin (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Kassubek, Jan (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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- Ludolph, Albert C. (författare)
- Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 90
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Amyotrophic lateral sclerosis
- Metabolic
- Metabolism
- Mutations carriers
- Presymptomatic
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Dorst, Johannes
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Weydt, Patrick
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Brenner, David
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Witzel, Simon
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Kandler, Kathari ...
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Huss, André
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Herrmann, Christ ...
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Wiesenfarth, Max ...
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Knehr, Antje
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Günther, Korneli ...
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Müller, Kathrin
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Weishaupt, Joche ...
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Prudlo, Johannes
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Forsberg, Karin
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Andersen, Peter ...
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Rosenbohm, Angel ...
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Schuster, Joachi ...
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Roselli, Frances ...
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Dupuis, Luc
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Mayer, Benjamin
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Tumani, Hayretti ...
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Kassubek, Jan
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Ludolph, Albert ...
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