{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:03:17Z","timestamp":1792782197031,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Denali Therapeutics","id":[{"id":"https:\/\/ror.org\/00pprn321","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      De\u2010identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0108; 85 with samples from \u22652 visits) and controls without neurological disease (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a041) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had\n                      <jats:italic>C9orf72<\/jats:italic>\n                      mutations. Additional healthy control CSF samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a035) were obtained from multiple sources. We stratified PALS into fast\u2010 and slow\u2010progression subgroups using the ALS Functional Rating Scale\u2010Revised change rate. We compared cytokines\/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with\n                      <jats:italic>C9orf72<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found significant elevations of cytokines, including MCP\u20101, IL\u201018, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast\u2010progression and\n                      <jats:italic>C9orf72<\/jats:italic>\n                      mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF\/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast\u2010progression patients and may be used to select similar patient subsets in clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51078","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T08:44:06Z","timestamp":1591692246000},"page":"1103-1116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Longitudinal biomarkers in amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-3789","authenticated-orcid":false,"given":"Fen","family":"Huang","sequence":"first","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuda","family":"Zhu","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hsiao\u2010Nakamoto","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Tang","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason C.","family":"Dugas","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Moscovitch\u2010Lopatin","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pathology Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert H.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Massachusetts Medical School Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafeeq S.","family":"Ladha","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Neurobiology Gregory W. Fulton ALS Center Barrow Neurological Institute Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lacomis","sequence":"additional","affiliation":[{"name":"Live Like Lou Center for ALS Research Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Harris","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Scearce\u2010Levie","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Ho","sequence":"additional","affiliation":[{"name":"Denali Therapeutics South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bowser","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Neurobiology Gregory W. Fulton ALS Center Barrow Neurological Institute Phoenix Arizona USA"},{"name":"Iron Horse Diagnostics, Inc. Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Berry","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.151"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.184"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2019.02.030"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.032"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70129-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30394-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)91680-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24979"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01167"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2007.01972.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24980"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001642"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0503-x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30285-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1646769"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004029"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-016-0689-x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03777.x"},{"key":"e_1_2_8_22_1","first-page":"12","article-title":"Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients","volume":"87","author":"Steinacker P","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00229"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1589-y"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000244"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.6179"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0051-1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.03.003"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1421666"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.04.006"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-94"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-21"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70015-1"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134523"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.01298"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.02.012"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112759"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316605"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.795"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99081"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001491"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.779"},{"key":"e_1_2_8_43_1","unstructured":"MillerTM CudkowiczME ShawPJ et al.Safety PK PD and exploratory efficacy in single and multiple dose study of a SOD1 antisense oligonucleotide (BIIB067) administered to participants with ALS. Poster session presented at: American Academy of Neurology Annual Meeting; 2019 May 4\u201310; Philadelphia PA."}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.51078","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51078","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51078","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T13:12:37Z","timestamp":1693833157000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/acn3.51078"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51078","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]},"assertion":[{"value":"2020-04-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}