Home > Publications Database > Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers. > print

001     257342
005     20240611120548.0
024 7 _ |a 10.1016/j.ebiom.2023.104521
|2 doi
024 7 _ |a pmid:36917918
|2 pmid
024 7 _ |a pmc:PMC10024076
|2 pmc
024 7 _ |a altmetric:143757743
|2 altmetric
037 _ _ |a DZNE-2023-00411
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Dorst, Johannes
|0 P:(DE-2719)9001951
|b 0
|u dzne
245 _ _ |a Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers.
260 _ _ |a Amsterdam [u.a.]
|c 2023
|b Elsevier
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1718027632_5322
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
500 _ _ |a CC BY-NC-ND
520 _ _ |a 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.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.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).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.This work was an investigator-initiated trial. On the German side, there was no institutional or industrial funding. On the Swedish side, this work was supported by grants from the Swedish Brain Foundation (grants nr. 2013-0279, 2016-0303, 2018-0310, 2020-0353), the Swedish Research Council (grants nr. 2012-3167, 2017-03100), the Knut and Alice Wallenberg Foundation (grants nr. 2012.0091, 2014.0305, 2020.0232), the Ulla-Carin Lindquist Foundation, Umeå University (223-2808-12, 223-1881-13, 2.1.12-1605-14) and the Västerbotten County Council (grants nr 56103-7002829), King Gustaf V:s and Queen Victoria's Freemason's Foundation.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 0
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 1
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a C9orf72 Protein
|2 NLM Chemicals
650 _ 7 |a Amyotrophic lateral sclerosis
|2 Other
650 _ 7 |a Metabolic
|2 Other
650 _ 7 |a Metabolism
|2 Other
650 _ 7 |a Mutations carriers
|2 Other
650 _ 7 |a Presymptomatic
|2 Other
650 _ 7 |a Superoxide Dismutase-1
|0 EC 1.15.1.1
|2 NLM Chemicals
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: diagnosis
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: genetics
|2 MeSH
650 _ 2 |a Intermediate Filaments
|2 MeSH
650 _ 2 |a C9orf72 Protein: genetics
|2 MeSH
650 _ 2 |a Superoxide Dismutase-1: genetics
|2 MeSH
650 _ 2 |a Biomarkers
|2 MeSH
700 1 _ |a Weydt, Patrick
|0 P:(DE-2719)9001116
|b 1
|u dzne
700 1 _ |a Brenner, David
|0 P:(DE-2719)9002137
|b 2
|u dzne
700 1 _ |a Witzel, Simon
|0 P:(DE-2719)9001976
|b 3
|u dzne
700 1 _ |a Kandler, Katharina
|b 4
700 1 _ |a Huss-Malejko, Andre
|0 P:(DE-2719)9002029
|b 5
|u dzne
700 1 _ |a Herrmann, Christine
|b 6
700 1 _ |a Wiesenfarth, Maximilian
|b 7
700 1 _ |a Knehr, Antje
|b 8
700 1 _ |a Günther, Kornelia
|b 9
700 1 _ |a Müller, Kathrin
|0 P:(DE-HGF)0
|b 10
700 1 _ |a Weishaupt, Jochen H
|0 P:(DE-HGF)0
|b 11
700 1 _ |a Prudlo, Johannes
|0 P:(DE-2719)2380559
|b 12
|u dzne
700 1 _ |a Forsberg, Karin
|b 13
700 1 _ |a Andersen, Peter M
|b 14
700 1 _ |a Rosenbohm, Angela
|0 P:(DE-HGF)0
|b 15
700 1 _ |a Schuster, Joachim
|0 P:(DE-2719)9002279
|b 16
|u dzne
700 1 _ |a Roselli, Francesco
|0 P:(DE-2719)2812851
|b 17
|u dzne
700 1 _ |a Dupuis, Luc
|b 18
700 1 _ |a Mayer, Benjamin
|b 19
700 1 _ |a Tumani, Hayrettin
|0 P:(DE-2719)9002007
|b 20
|u dzne
700 1 _ |a Kassubek, Jan
|0 P:(DE-2719)9001967
|b 21
|u dzne
700 1 _ |a Ludolph, Albert C
|0 P:(DE-2719)2812633
|b 22
|e Last author
|u dzne
773 _ _ |a 10.1016/j.ebiom.2023.104521
|g Vol. 90, p. 104521 -
|0 PERI:(DE-600)2799017-5
|p 104521
|t EBioMedicine
|v 90
|y 2023
|x 2352-3964
856 4 _ |u https://pub.dzne.de/record/257342/files/DZNE-2023-00411%20SUP.doc
856 4 _ |u https://pub.dzne.de/record/257342/files/DZNE-2023-00411%20SUP.docx
856 4 _ |u https://pub.dzne.de/record/257342/files/DZNE-2023-00411%20SUP.odt
856 4 _ |u https://pub.dzne.de/record/257342/files/DZNE-2023-00411%20SUP.pdf
856 4 _ |u https://pub.dzne.de/record/257342/files/DZNE-2023-00411.pdf
|y OpenAccess
856 4 _ |u https://pub.dzne.de/record/257342/files/DZNE-2023-00411.pdf?subformat=pdfa
|x pdfa
|y OpenAccess
909 C O |o oai:pub.dzne.de:257342
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)9001951
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 1
|6 P:(DE-2719)9001116
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 2
|6 P:(DE-2719)9002137
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 3
|6 P:(DE-2719)9001976
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 5
|6 P:(DE-2719)9002029
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 12
|6 P:(DE-2719)2380559
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 16
|6 P:(DE-2719)9002279
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 17
|6 P:(DE-2719)2812851
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 20
|6 P:(DE-2719)9002007
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 21
|6 P:(DE-2719)9001967
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 22
|6 P:(DE-2719)2812633
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 0
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 1
914 1 _ |y 2023
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
|0 LIC:(DE-HGF)CCBYNCND4
|2 HGFVOC
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2022-11-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2022-11-25
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2022-11-25
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2022-11-25
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b EBIOMEDICINE : 2022
|d 2023-08-26
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-26
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-26
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-08-26
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2023-05-02T08:51:17Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2023-05-02T08:51:17Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Anonymous peer review
|d 2023-05-02T08:51:17Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-26
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-26
915 _ _ |a IF >= 10
|0 StatID:(DE-HGF)9910
|2 StatID
|b EBIOMEDICINE : 2022
|d 2023-08-26
920 1 _ |0 I:(DE-2719)5000077
|k Clinical Study Center Ulm
|l Clinical Study Center Ulm
|x 0
920 1 _ |0 I:(DE-2719)1510100
|k AG Teipel
|l Clinical Dementia Research (Rostock /Greifswald)
|x 1
920 1 _ |0 I:(DE-2719)1910001
|k AG Roselli
|l Metabolic Changes in Neurodegeneration
|x 2
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)5000077
980 _ _ |a I:(DE-2719)1510100
980 _ _ |a I:(DE-2719)1910001
980 _ _ |a UNRESTRICTED
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21