{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:43:52Z","timestamp":1793331832860,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006129","name":"Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reliable biomarkers for amyotrophic lateral sclerosis (ALS) are urgently needed due to diagnostic and prognostic challenges. This systematic review and meta\u2010analysis aimed to synthesize recent evidence on the utility of blood and cerebrospinal fluid (CSF) biomarkers for ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically reviewed studies published from January 1, 2019 to March 25, 2025, that evaluated blood or CSF biomarkers for ALS. Eligible studies reported diagnostic performance, group\u2010level biomarker values, hazard ratios (HRs) for survival, or correlations with functional rating scales\u00a0or disease progression rates. Study quality was assessed using the QUADAS\u20102 and QUIPS frameworks. Random\u2010effects models were employed to pool summary receiver operating characteristic (SROC) curves, HRs, standardized mean differences, and correlation coefficients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 47 studies in the SROC analysis and 27 in the HR analysis, covering 9078 participants (5556 ALS and 3522 controls). Neurofilament light chain (NfL) consistently demonstrated the highest diagnostic accuracy (sensitivity\/specificity: 0.81\u20130.87 vs. ALS mimics) and high prognostic value (pooled HRs: 2.8\u20134.3) in both blood and CSF. CSF chitinases and the p\u2010tau\/t\u2010tau ratio showed moderate utility. Other biomarkers, including interleukins, had limited clinical relevance. Most studies showed moderate to high risk of bias, with methodological heterogeneity and limited transparency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NfL is the most validated biomarker for ALS diagnosis and prognosis, in both blood and CSF. However, its limited accuracy when used alone carries a considerable risk of misclassification. Future studies should adopt prevalence\u2010specific strategies and integrate biomarkers within\u00a0multimodal frameworks to enhance diagnostic and prognostic precision.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70382","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T07:22:52Z","timestamp":1761549772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Diagnostic and Prognostic Value of Blood and Cerebrospinal Fluid Biomarkers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5170-9169","authenticated-orcid":false,"given":"Kazuki","family":"Obara","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6 Lund University  Lund Sweden"},{"name":"Department of Neurology Nagoya University 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