{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:07:07Z","timestamp":1784603227457,"version":"3.55.0"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007030","name":"Les Turner ALS Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. Super oxide dismutase 1 (\n                      <jats:italic>SOD1<\/jats:italic>\n                      ) gene mutations cause ALS, and the\n                      <jats:italic>D90A<\/jats:italic>\n                      mutation is associated with primarily upper motor neuron (UMN) loss.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our goal is to reveal the early cellular events in ALS pathology and identify potential pharmacokinetic biomarkers, using well\u2010defined patient populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Exosomes are isolated from serum either single or multiple time points from members of one family, who have SOD1\n                      <jats:sup>D90A<\/jats:sup>\n                      mutation, and their protein content is assessed by tandem mass\u2010spec proteomics. Ingenuity Pathway analysis is used to highlight cellular events that are perturbed as the disease progressed. The linear regression analysis, using ALSFRS scores of patients and the protein content, helps identify potential pharmacokinetic biomarkers, which are confirmed with the ELISA assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Father, Son, and Daughter are at different disease stages and carry the SOD1\n                      <jats:sup>D90A<\/jats:sup>\n                      mutation. Albeit, the Daughter remained asymptomatic within a year; she had significant biological changes. The Son transitioned from asymptomatic to early symptomatic within a year, while the Father was symptomatic. Patient #2, who also had the SOD1\n                      <jats:sup>D90A<\/jats:sup>\n                      mutation, was more advanced. Comparison of the Son, Father, and Patient #2 suggested Fibronectin1 (FN1) as a potential pharmacokinetic biomarker, which is confirmed by ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Exosome proteomics offer a powerful approach to interrogate disease\u2010specific or disease\u2010related proteins that become present in the blood. This helps define the perturbed cellular events with respect to disease progression and reveal potential pharmacokinetic biomarkers. We find FN1 levels to increase with disease progression, suggesting it may be a pharmacokinetic biomarker, especially for ALS patients with prominent UMN loss.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70208","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T04:25:24Z","timestamp":1759206324000},"page":"131-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exosome Proteomics of\n                    <scp>\n                      SOD1\n                      <sup>D90A<\/sup>\n                    <\/scp>\n                    Mutation Suggest Early Disease Mechanisms, and\n                    <scp>FN1<\/scp>\n                    as a Biomarker"],"prefix":"10.1002","volume":"13","author":[{"given":"Mukesh","family":"Gautam","sequence":"first","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Laith","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslihan","family":"Gunel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Kirsehir Ahi Evran University  Kirsehir Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melda","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Medical Sciences Department Kocaeli University  Izmit Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6977-2517","authenticated-orcid":false,"given":"Nazli","family":"Basak","sequence":"additional","affiliation":[{"name":"School of Medicine, KUTTAM\u2010NDAL Koc University  Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halil","family":"Idrisoglu","sequence":"additional","affiliation":[{"name":"School of Medicine Department of Neurology, Istanbul University  Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-6013","authenticated-orcid":false,"given":"P. Hande","family":"Ozdinler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"},{"name":"Feinberg School of Medicine Les Turner ALS Center, Northwestern University  Chicago Illinois USA"},{"name":"Chemistry of Life Processes Institute Northwestern University  Evanston Illinois USA"},{"name":"Feinberg School of Medicine Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024117"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11030369"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00592-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32902-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/362059a0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(96)00084-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22157"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/17482960802146106"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-009-0125-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-04956-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5053-11.2012"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-023-00419-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.12.003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01904-6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-021-00730-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.03.017"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14274"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.21037\/tcr.2019.01.03"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/17434470410019906"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2021.1900259"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8538-4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3791\/63816"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.140"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3524-6_18"},{"issue":"7","key":"e_1_2_9_26_1","first-page":"388","article-title":"Mass Spectrometry Accelerates Membrane Protein Analysis","volume":"36","author":"Savas J. 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