{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:47:19Z","timestamp":1789804039435,"version":"4.0.1"},"reference-count":30,"publisher":"Walter de Gruyter GmbH","issue":"11","funder":[{"DOI":"10.13039\/100007403","name":"Dagmar Marshalls Fond","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007403","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008262","name":"Harboefonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2022-0480_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker for intracerebral diseases and is approved for clinical use in traumatic brain injury. GFAP is also being investigated for several other applications, where the GFAP changes are not always outstanding. It is thus essential for the interpretation of GFAP to distinguish clinical relevant changes from natural occurring biological variation. This study aimed at estimating the biological variation of serum GFAP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0480_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Apparently healthy subjects (n=33) had blood sampled for three consecutive days. On the second day, blood was also drawn every third hour from 9 AM to 9 PM. Serum GFAP was measured by Single Molecule Array (Simoa\u2122). Components of biological variation were estimated in a linear mixed-effects model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0480_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The overall median GFAP value was 92.5\u00a0pg\/mL (range 34.4\u2013260.3\u00a0pg\/mL). The overall within\u2013 (CV<jats:sub>I<\/jats:sub>) and between-subject variations (CV<jats:sub>G<\/jats:sub>) were 9.7 and 39.5%. The reference change value was 36.9% for an increase. No day-to-day variation was observed, however semidiurnal variation was observed with increasing GFAP values between 9\u00a0AM and 12 PM (p&lt;0.00001) and decreasing from 12 to 9 PM (p&lt;0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0480_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Serum GFAP exhibits a relatively low CV<jats:sub>I<\/jats:sub> but a considerable CV<jats:sub>G<\/jats:sub> and a marked semidiurnal variation. This implies caution on the timing of blood sampling and when interpreting GFAP in relation to reference intervals, especially in conditions where only small GFAP differences are observed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2022-0480","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T09:08:08Z","timestamp":1660381688000},"page":"1813-1819","source":"Crossref","is-referenced-by-count":13,"title":["Short-term biological variation of serum glial fibrillary acidic protein"],"prefix":"10.1515","volume":"60","author":[{"given":"Silje Hovden","family":"Christensen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Vinter B\u00f8dker","family":"Hviid","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Biochemistry , Aalborg University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine , Aarhus University , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9146-5943","authenticated-orcid":false,"given":"Anne Tranberg","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , New York , NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Parkner","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine , Aarhus University , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Winther-Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine , Aarhus University , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"2023033113340227670_j_cclm-2022-0480_ref_001","doi-asserted-by":"crossref","unstructured":"Yang, Z, Wang, KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 2015;38:364\u201374. https:\/\/doi.org\/10.1016\/j.tins.2015.04.003.","DOI":"10.1016\/j.tins.2015.04.003"},{"key":"2023033113340227670_j_cclm-2022-0480_ref_002","doi-asserted-by":"crossref","unstructured":"Messing, A, Brenner, M. GFAP at 50. ASN Neuro 2020;12:1759091420949680. https:\/\/doi.org\/10.1177\/1759091420949680.","DOI":"10.1177\/1759091420949680"},{"key":"2023033113340227670_j_cclm-2022-0480_ref_003","doi-asserted-by":"crossref","unstructured":"Abdelhak, A, Foschi, M, Abu-Rumeileh, S, Yue, JK, D\u2019Anna, L, Huss, A, et al.. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol 2022;18:158\u201372. https:\/\/doi.org\/10.1038\/s41582-021-00616-3.","DOI":"10.1038\/s41582-021-00616-3"},{"key":"2023033113340227670_j_cclm-2022-0480_ref_004","doi-asserted-by":"crossref","unstructured":"Kim, R, Healey, KL, Sepulveda-Orengo, MT, Reissner, KJ. Astroglial correlates of neuropsychiatric disease: from astrocytopathy to astrogliosis. Prog Neuro-Psychopharmacol Biol Psychiatry 2018;87:126\u201346. https:\/\/doi.org\/10.1016\/j.pnpbp.2017.10.002.","DOI":"10.1016\/j.pnpbp.2017.10.002"},{"key":"2023033113340227670_j_cclm-2022-0480_ref_005","doi-asserted-by":"crossref","unstructured":"Janigro, D, Mondello, S, Posti, JP, Unden, J. GFAP and S100B: what you always wanted to know and never dared to ask. Front Neurol 2022;13:835597. https:\/\/doi.org\/10.3389\/fneur.2022.835597.","DOI":"10.3389\/fneur.2022.835597"},{"key":"2023033113340227670_j_cclm-2022-0480_ref_006","doi-asserted-by":"crossref","unstructured":"Benedet, AL, Mila-Aloma, M, Vrillon, A, Ashton, NJ, Pascoal, TA, Lussier, F, et al.. Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the alzheimer disease continuum. JAMA Neurol 2021;78:1471\u201383. https:\/\/doi.org\/10.1001\/jamaneurol.2021.3671.","DOI":"10.1001\/jamaneurol.2021.3671"},{"key":"2023033113340227670_j_cclm-2022-0480_ref_007","doi-asserted-by":"crossref","unstructured":"Michel, M, Fiebich, BL, Kuzior, H, Meixensberger, S, Berger, B, Maier, S, et al.. Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression. 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