{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:10:16Z","timestamp":1790878216161,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ibroneuroreports.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["IBRO Neuroscience Reports"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.ibneur.2026.02.006","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:35:17Z","timestamp":1770338117000},"page":"227-231","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case\u2013control study"],"prefix":"10.1016","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3717-3437","authenticated-orcid":false,"given":"Salvatore","family":"Sotgia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-0968","authenticated-orcid":false,"given":"Angelo","family":"Zinellu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Zoroddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-9694","authenticated-orcid":false,"given":"Maria Ida","family":"Pateri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Loi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-6161","authenticated-orcid":false,"given":"Angela","family":"Sabalic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4515-1885","authenticated-orcid":false,"given":"Davide","family":"Tutedde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Florencia","family":"Vega-Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Floris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6837-6608","authenticated-orcid":false,"given":"Monica","family":"Puligheddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6812-5921","authenticated-orcid":false,"given":"Paolo","family":"Valera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Zavattari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Borghero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Madeddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ibneur.2026.02.006_bib1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3390\/life15040647","article-title":"Pathophysiology, clinical heterogeneity, and therapeutic advances in amyotrophic lateral sclerosis: a comprehensive review of molecular mechanisms, diagnostic challenges, and multidisciplinary management strategies","volume":"15","author":"Gonz\u00e1lez-S\u00e1nchez","year":"2025","journal-title":"Life"},{"key":"10.1016\/j.ibneur.2026.02.006_bib2","first-page":"181","article-title":"Risk factors for amyotrophic lateral sclerosis","volume":"7","author":"Ingre","year":"2015","journal-title":"Clin. Epidemiol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.neurol.2024.10.005","article-title":"Quantitative spinal cord imaging: early ALS diagnosis and monitoring of disease progression","volume":"181","author":"Khamaysa","year":"2025","journal-title":"Rev. Neurol. (Paris)"},{"key":"10.1016\/j.ibneur.2026.02.006_bib4","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: a clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib5","doi-asserted-by":"crossref","first-page":"17786","DOI":"10.1038\/s41598-019-54372-y","article-title":"Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis and its differential diagnosis value","volume":"9","author":"Hu","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ibneur.2026.02.006_bib6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1080\/21678421.2019.1612435","article-title":"Clinical characteristics of a large cohort of US participants enrolled in the National Amyotrophic Lateral Sclerosis (ALS) Registry, 2010\u20132015","volume":"20","author":"Raymond","year":"2019","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"10.1016\/j.ibneur.2026.02.006_bib7","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2021.596006","article-title":"Destination amyotrophic lateral sclerosis","volume":"12","author":"Keon","year":"2021","journal-title":"Front Neurol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/2152-7806.169561","article-title":"A comprehensive review of amyotrophic lateral sclerosis","volume":"6","author":"Zarei","year":"2015","journal-title":"Surg. Neurol. Int"},{"key":"10.1016\/j.ibneur.2026.02.006_bib9","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3109\/17482960802566824","article-title":"Prognostic factors in ALS: a critical review","volume":"10","author":"Chi\u00f2","year":"2009","journal-title":"Amyotroph. Lateral Scler."},{"key":"10.1016\/j.ibneur.2026.02.006_bib10","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000213467","article-title":"Changes to average survival of patients with amyotrophic lateral sclerosis (1995\u20132018): results from the Piemonte and Valle d\u2019Aosta registry","volume":"104","author":"Vasta","year":"2025","journal-title":"Neurology"},{"key":"10.1016\/j.ibneur.2026.02.006_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103795","article-title":"Unraveling the complex interplay between genes, environment, and climate in ALS","volume":"75","author":"Vasta","year":"2022","journal-title":"EBioMedicine"},{"key":"10.1016\/j.ibneur.2026.02.006_bib12","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/WCO.0000000000001294","article-title":"The genetics of amyotrophic lateral sclerosis","volume":"37","author":"Nijs","year":"2024","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40035-024-00416-x","article-title":"Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications","volume":"13","author":"Huang","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.ibneur.2026.02.006_bib14","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1007\/s13311-015-0338-x","article-title":"TDP-43 proteinopathy and ALS: insights into disease mechanisms and therapeutic targets","volume":"12","author":"Scotter","year":"2015","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.ibneur.2026.02.006_bib15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13024-020-00397-1","article-title":"The role of TDP-43 mislocalization in amyotrophic lateral sclerosis","volume":"15","author":"Suk","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.ibneur.2026.02.006_bib16","article-title":"Pathogenic TDP-43 in amyotrophic lateral sclerosis","volume":"30","author":"Zhao","year":"2025","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ibneur.2026.02.006_bib17","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1177431","article-title":"Risk factors of amyotrophic lateral sclerosis: a global meta-summary","volume":"17","author":"Duan","year":"2023","journal-title":"Front Neurosci."},{"key":"10.1016\/j.ibneur.2026.02.006_bib18","article-title":"Environmental risk factors and amyotrophic lateral sclerosis (ALS): a case-control study of ALS in Michigan","volume":"9","author":"Yu","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ibneur.2026.02.006_bib19","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.3390\/foods10123128","article-title":"Amyotrophic lateral sclerosis: a diet review","volume":"10","author":"D\u2019Antona","year":"2021","journal-title":"Foods"},{"key":"10.1016\/j.ibneur.2026.02.006_bib20","doi-asserted-by":"crossref","first-page":"23497","DOI":"10.1038\/s41598-024-75083-z","article-title":"Examining the complex interplay between gut microbiota abundance and short-chain fatty acid production in amyotrophic lateral sclerosis patients shortly after onset of disease","volume":"14","author":"Fontdevila","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ibneur.2026.02.006_bib21","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1085041","article-title":"The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases","volume":"14","author":"Zhen","year":"2023","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"10.1016\/j.ibneur.2026.02.006_bib22","first-page":"301","article-title":"Trimethylamine N-oxide (TMAO) in human health","volume":"20","author":"Gatarek","year":"2021","journal-title":"EXCLI J."},{"key":"10.1016\/j.ibneur.2026.02.006_bib23","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2022.964624","article-title":"Implications of trimethylamine N-oxide (TMAO) and betaine in human health: beyond being osmoprotective compounds","volume":"9","author":"Ilyas","year":"2022","journal-title":"Front Mol. Biosci."},{"key":"10.1016\/j.ibneur.2026.02.006_bib24","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.99096","article-title":"Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk","volume":"3","author":"Li","year":"2018","journal-title":"JCI Insight"},{"key":"10.1016\/j.ibneur.2026.02.006_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0161074","article-title":"Association of FMO3 variants and trimethylamine N-oxide concentration, disease progression, and mortality in CKD patients","volume":"11","author":"Robinson-Cohen","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ibneur.2026.02.006_bib26","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s10020-024-00895-8","article-title":"Trimethylamine N-oxide: a meta-organismal axis linking the gut and fibrosis","volume":"30","author":"Jang","year":"2024","journal-title":"Mol. Med"},{"key":"10.1016\/j.ibneur.2026.02.006_bib27","article-title":"The impact of chronic trimethylamine N-oxide administration on liver oxidative stress, inflammation, and fibrosis","volume":"184","author":"Cristian","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib28","doi-asserted-by":"crossref","first-page":"15198","DOI":"10.1038\/s41598-020-72184-3","article-title":"Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis","volume":"10","author":"Chen","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ibneur.2026.02.006_bib29","first-page":"293","article-title":"El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis","volume":"1","author":"Brooks","year":"2000","journal-title":"Amyotroph. Lateral Scler."},{"key":"10.1016\/j.ibneur.2026.02.006_bib30","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1136\/jnnp.2010.235952","article-title":"Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population-based study","volume":"82","author":"Chi\u00f2","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.ibneur.2026.02.006_bib31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/brain\/awr351","article-title":"A proposed staging system for amyotrophic lateral sclerosis","volume":"135","author":"Roche","year":"2012","journal-title":"Brain"},{"key":"10.1016\/j.ibneur.2026.02.006_bib32","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1080\/21678421.2016.1183679","article-title":"The validation of the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS)","volume":"17","author":"Poletti","year":"2016","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"10.1016\/j.ibneur.2026.02.006_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.cca.2025.120294","article-title":"Quantification of trimethylamine-N-oxide (TMAO) and its main related trimethylammonium-containing compounds in human plasma by LC-MS\/MS","volume":"573","author":"Sotgia","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.ibneur.2026.02.006_bib34","doi-asserted-by":"crossref","first-page":"9451","DOI":"10.3390\/ijms21249451","article-title":"Trimethyllysine: from carnitine biosynthesis to epigenetics","volume":"21","author":"Maas","year":"2020","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.ibneur.2026.02.006_bib35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/iub.323","article-title":"Enzymology of the carnitine biosynthesis pathway","volume":"62","author":"Strijbis","year":"2010","journal-title":"IUBMB Life"},{"key":"10.1016\/j.ibneur.2026.02.006_bib36","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3390\/metabo14070356","article-title":"Disturbances in muscle energy metabolism in patients with amyotrophic lateral sclerosis","volume":"14","author":"Parvanovova","year":"2024","journal-title":"Metabolites"},{"key":"10.1016\/j.ibneur.2026.02.006_bib37","doi-asserted-by":"crossref","DOI":"10.1002\/imt2.183","article-title":"Unraveling interindividual variation of trimethylamine N-oxide and its precursors at the population level","volume":"3","author":"Andreu-S\u00e1nchez","year":"2024","journal-title":"iMeta"},{"key":"10.1016\/j.ibneur.2026.02.006_bib38","doi-asserted-by":"crossref","DOI":"10.1080\/0886022X.2024.2435485","article-title":"Research progress on the association between TMAO and vascular calcification in patients with chronic kidney disease","volume":"46","author":"Zhang","year":"2024","journal-title":"Ren. Fail"},{"key":"10.1016\/j.ibneur.2026.02.006_bib39","doi-asserted-by":"crossref","DOI":"10.1080\/07853890.2025.2525403","article-title":"Trimethylamine-N-oxide formation, the bacterial taxa involved, and intervention strategies to reduce its concentration in the human body","volume":"57","author":"Heinrich-Sanchez","year":"2025","journal-title":"Ann. Med"},{"key":"10.1016\/j.ibneur.2026.02.006_bib40","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3390\/metabo15040220","article-title":"Trimethylamine-N-oxide (TMAO) as a rising-star metabolite: implications for human health","volume":"15","author":"Caradonna","year":"2025","journal-title":"Metabolites"},{"key":"10.1016\/j.ibneur.2026.02.006_bib41","article-title":"Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis","volume":"16","author":"Long","year":"2024","journal-title":"Front Aging Neurosci."},{"key":"10.1016\/j.ibneur.2026.02.006_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105884","article-title":"Unraveling the metabolic pathway of choline\u2013TMA\u2013TMAO: effects of gypenosides and implications for therapy of TMAO-related diseases","volume":"173","author":"Zhang","year":"2021","journal-title":"Pharm. Res"},{"key":"10.1016\/j.ibneur.2026.02.006_bib43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s40168-021-01181-z","article-title":"Regulation of blood\u2013brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide","volume":"9","author":"Hoyles","year":"2021","journal-title":"Microbiome"},{"key":"10.1016\/j.ibneur.2026.02.006_bib44","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13195-018-0451-2","article-title":"The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer's disease","volume":"10","author":"Vogt","year":"2018","journal-title":"Alzheimers Res Ther."},{"key":"10.1016\/j.ibneur.2026.02.006_bib45","doi-asserted-by":"crossref","first-page":"8476","DOI":"10.1073\/pnas.1403224111","article-title":"Microscopic insights into the protein-stabilizing effect of trimethylamine N-oxide (TMAO)","volume":"111","author":"Ma","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ibneur.2026.02.006_bib46","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/s41589-024-01568-7","article-title":"In situ analysis of osmolyte mechanisms of proteome thermal stabilization","volume":"20","author":"Pepelnjak","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib47","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S1047-8477(02)00513-0","article-title":"Effects of the osmolyte trimethylamine-N-oxide on conformation, self-association, and two-dimensional crystallization of myelin basic protein","volume":"139","author":"Hill","year":"2002","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.ibneur.2026.02.006_bib48","doi-asserted-by":"crossref","first-page":"6822","DOI":"10.1021\/acs.biochem.8b01051","article-title":"A chemical chaperone decouples TDP-43 disordered domain phase separation from fibrillation","volume":"57","author":"Choi","year":"2018","journal-title":"Biochemistry"},{"key":"10.1016\/j.ibneur.2026.02.006_bib49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fnmol.2020.00019","article-title":"Chaperone-mediated autophagy degrades TDP-43 protein and is affected by TDP-43 aggregation","volume":"13","author":"Orme\u00f1o","year":"2020","journal-title":"Front Mol. Neurosci."}],"container-title":["IBRO Neuroscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667242126000230?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667242126000230?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T20:19:44Z","timestamp":1782159584000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2667242126000230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":49,"alternative-id":["S2667242126000230"],"URL":"https:\/\/doi.org\/10.1016\/j.ibneur.2026.02.006","relation":{},"ISSN":["2667-2421"],"issn-type":[{"value":"2667-2421","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case\u2013control study","name":"articletitle","label":"Article Title"},{"value":"IBRO Neuroscience Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ibneur.2026.02.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc. on behalf of International Brain Research Organization.","name":"copyright","label":"Copyright"}]}}