{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:46:39Z","timestamp":1785833199763,"version":"3.56.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Council","award":["577 631"],"award-info":[{"award-number":["577 631"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including a pronounced increase in Alzheimer disease (AD). However, GFAP levels in the serum also increase with age. Consequently, the integration of GFAP levels into clinical routine and their interpretation demands age-adjusted reference values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum from 1273 subjects (952 noninflammatory and nonneurodegenerative neurological controls and 321 subjects with AD) was analyzed for GFAP using the microfluidic Ella system. Age-dependent serum GFAP reference values were estimated by additive quantile regression analysis and visualized with percentiles and z-scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AD exhibited elevated serum GFAP levels in comparison to control patients (P &amp;lt; 0.0001). This remained the case when the newly generated age-corrected z-scores were applied (P &amp;lt; 0.0001). In the control cohort, a nonlinear elevation of serum GFAP with increasing age was observed (Spearman correlation coefficient 0.62, 95% CI 0.58\u20130.66, P &amp;lt; 0.0001). In contrast, the AD cohort exhibited a more linear increase (0.16, 95% CI 0.05\u20130.26, P = 0.004). Age-dependent cut-offs for serum GFAP were determined for different AD age groups. The calculated areas under the curve (AUCs; 0.97) demonstrated excellent diagnostic test performance in the early-onset age group. This effect was less marked in the elderly subjects (AUC 0.72).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our novel GFAP z-scores enable the integration and interpretation of serum GFAP levels in clinical practice, moving from the group to individual level. They support both intra- and interindividual interpretation of single GFAP levels in neurological diseases with astrocytic pathology, including an accurate discrimination of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaf120","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T12:02:13Z","timestamp":1758283333000},"page":"1234-1242","source":"Crossref","is-referenced-by-count":8,"title":["Age-Specific Control and Alzheimer Disease Reference Curves and\n                    <i>z<\/i>\n                    -Scores for Glial Fibrillary Acidic Protein in Blood"],"prefix":"10.1093","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-5702","authenticated-orcid":false,"given":"Steffen","family":"Halbgebauer","sequence":"first","affiliation":[{"name":"Department of Neurology, Ulm University Hospital , Ulm ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases , Ulm 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,","place":["Germany"]},{"name":"Department of Neurology, University Hospital Halle , Halle (Saale) ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G Bernhard","family":"Landwehrmeyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University Hospital , Ulm ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-4169","authenticated-orcid":false,"given":"Ahmed","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, University of California at San Francisco , San Francisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-9749","authenticated-orcid":false,"given":"Axel","family":"Petzold","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Queen Square Institute of 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