{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:58:43Z","timestamp":1791197923777,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the association and discriminative performance of serum biomarkers with clinical disease progression and survival in patients with amyotrophic lateral sclerosis (ALS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study, conducted at Houston Methodist Hospital, Houston, TX, used longitudinal serum samples collected between January 2018 and December 2022. A cohort of 100 patients with sporadic or familial ALS was randomly selected and assayed by ELISAs for biomarkers 4\u2010hydroxy\u20102\u2010nonenal (4\u2010HNE), lipopolysaccharide binding protein (LBP), and neurofilament light chain (NfL) levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Each biomarker was increased in patients. 4\u2010HNE and LBP were increased at diagnosis and continued to increase as the disease progressed; both correlated with progression rates and survival. NfL was increased at diagnosis, then plateaued relatively. LBP correlated with ALSFRS\u2010R at diagnosis; NfL did not correlate. 4\u2010HNE and LBP were increased in bulbar onset patients who survived a shorter period of time; NfL levels for bulbar\/limb onsets were not different. Receiver operating characteristic analyses with apparent and optimism\u2010adjusted area\u2010under\u2010the\u2010curve (AUC) demonstrated that 4\u2010HNE and LBP discriminated rapid progression and survival, whereas NfL showed modest discrimination for rapid progression. The combination of biomarkers yielded improved AUCs as depicted in Venn diagrams across individual and combined biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>4\u2010HNE, LBP, and NfL are biomarkers of lipid peroxidation, systemic inflammation, and axonal integrity. 4\u2010HNE and LBP correlated with disease burden, disease progression, and survival. In the bulbar onset, survival was shortened and associated with increased 4\u2010HNE and LBP. This exploratory longitudinal study suggests the utility of combining biomarkers to discriminate disease progression and survival and monitor clinical trial outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70381","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T03:53:58Z","timestamp":1775534038000},"page":"2102-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Assessment of Biomarkers in\n                    <scp>ALS<\/scp>\n                    : Discriminative Biomarkers for Disease Progression and Survival"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8757-3500","authenticated-orcid":false,"given":"David R.","family":"Beers","sequence":"first","affiliation":[{"name":"Peggy and Gary Edwards ALS Laboratory, Stanley H. 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