{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T19:59:25Z","timestamp":1773777565157,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FUJIREBIO INC."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glial fibrillary acidic protein (GFAP) has been shown to be a reliable biomarker for detecting neurological disorders. Recently, we developed the Lumipulse G GFAP plasma assay, which is a commercially available tool. Compared to existing assays, the LUMIPLSE G platform offers the high-throughput, rapid, and fully automated quantification of biomarkers, enabling more standardized and accessible clinical study. In this study, we evaluated this assay using cerebrospinal fluid (CSF) samples. Assessing GFAP in CSF may provide more direct insights into central nervous system pathology than plasma and could improve the characterization of Alzheimer\u2019s disease (AD) stages and support treatment monitoring. The LUMIPULSE G system is a chemiluminescent enzyme immunoassay (CLEIA) platform equipped with full automation, utilizing specialized cartridges to process samples within 30 min. The assay, which employs a pair of proprietary monoclonal antibodies targeting GFAP, was evaluated for clinical performance using 30 CSF samples from patients diagnosed with AD, patients with mild cognitive impairment (MCI), and cognitively unimpaired (CU) individuals, with 10 samples from each group. In addition, levels of \u03b2-amyloid 1\u201340 (A\u03b240), \u03b2-amyloid 1\u201342 (A\u03b242), and pTau181 were simultaneously measured. The Lumipulse G GFAP assay significantly differentiated (p &lt; 0.05) between the amyloid accumulation and non-amyloid accumulation groups, as classified based on the CSF A\u03b2 test. Furthermore, GFAP showed a moderate correlation with pTau181 (r = 0.588), as determined based on Spearman\u2019s rank correlation coefficient. Moreover, receiver operating characteristic (ROC) analysis was performed to determine the performance of GFAP in distinguishing amyloid-positive and amyloid-negative subjects, with an area under the curve (AUC) of 0.72 (0.50\u20130.93). When stratified by CSF pTau181 positivity, GFAP demonstrated an improved diagnostic accuracy, achieving an AUC of 0.86 (95% CI: 0.68\u20131.00). This study demonstrates that the Lumipulse G GFAP assay, when applied to CSF samples, has the potential to differentiate AD from non-AD cases, particularly suggesting its utility in detecting tau-related pathology. While GFAP has previously been established as a biomarker for AD, our findings highlight that combining GFAP with other biomarkers such as A\u03b240, A\u03b242, and pTau181 may enhance the understanding of AD pathogenesis, disease staging, and possibly treatment responses. These findings suggest that GFAP may serve as a complementary biomarker reflecting astroglial reactivity associated with tau positivity, alongside established biomarkers such as A\u03b240, A\u03b242, and pTau181. However, since GFAP levels may also be elevated in other neurological disorders beyond AD, further investigation into these conditions is required.<\/jats:p>","DOI":"10.3390\/ijms26178134","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:31:26Z","timestamp":1755865886000},"page":"8134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fully Automated Measurement of GFAP in CSF Using the LUMIPULSE\u00ae System: Implications for Alzheimer\u2019s Disease Diagnosis and Staging"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8907-5767","authenticated-orcid":false,"given":"Hisashi","family":"Nojima","sequence":"first","affiliation":[{"name":"FUJIREBIO INC., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"FUJIREBIO INC., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo","family":"Kamada","sequence":"additional","affiliation":[{"name":"FUJIREBIO INC., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Hamanaka","sequence":"additional","affiliation":[{"name":"FUJIREBIO INC., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsumi","family":"Aoyagi","sequence":"additional","affiliation":[{"name":"FUJIREBIO INC., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(2024). Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 20, 3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1474-4422(21)00361-6","article-title":"Blood-based biomarkers for Alzheimer\u2019s disease: Towards clinical implementation","volume":"21","author":"Teunissen","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"fcae396","DOI":"10.1093\/braincomms\/fcae396","article-title":"Glial fibrillary acidic protein in Alzheimer\u2019s disease: A narrative review","volume":"6","author":"Leipp","year":"2024","journal-title":"Brain Commun."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Perez-Nievas, B.G., and Serrano-Pozo, A. (2018). Deciphering the Astrocyte Reaction in Alzheimer\u2019s Disease. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00114"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1001\/jamaneurol.2022.3392","article-title":"Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial","volume":"79","author":"Pontecorvo","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1002\/acn3.51681","article-title":"Clinical utility of cerebrospinal fluid biomarkers measured by LUMIPULSE((R)) system","volume":"9","author":"Nojima","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tips.2015.03.002","article-title":"Amyloid biomarkers in Alzheimer\u2019s disease","volume":"36","author":"Blennow","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1001\/jamaneurol.2021.3671","article-title":"Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum","volume":"78","author":"Benedet","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13195-021-00804-9","article-title":"Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment","volume":"13","author":"Cicognola","year":"2021","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102485","DOI":"10.1016\/j.arr.2024.102485","article-title":"CSF and blood glial fibrillary acidic protein for the diagnosis of Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"101","author":"Zou","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kamada, J., Hamanaka, T., Oshimo, A., Sato, H., Nishii, T., Fujita, M., Makiguchi, Y., Tanaka, M., Aoyagi, K., and Nojima, H. (2024). Glial Fibrillary Acidic Protein\u2019s Usefulness as an Astrocyte Biomarker Using the Fully Automated LUMIPULSE(\u00ae) System. Diagnostics, 14.","DOI":"10.3390\/diagnostics14222520"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.37349\/en.2023.00024","article-title":"Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE\u00ae assays","volume":"2","author":"Yuri","year":"2023","journal-title":"Explor. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1038\/s41591-025-03622-w","article-title":"Plasma phospho-tau217 for Alzheimer\u2019s disease diagnosis in primary and secondary care using a fully automated platform","volume":"31","author":"Palmqvist","year":"2025","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.2967\/jnumed.116.185017","article-title":"Clinical Use and Utility of Amyloid Imaging","volume":"58","author":"Barthel","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2032s Dement."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/jnc.13399","article-title":"Glial fibrillar acidic protein in the cerebrospinal fluid of Alzheimer\u2019s disease, dementia with Lewy bodies, and frontotemporal lobar degeneration","volume":"136","author":"Ishiki","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_19","first-page":"2","article-title":"CSF biomarkers of neuroinflammation in distinct forms and subtypes of neurodegenerative dementia","volume":"12","author":"Steinacker","year":"2019","journal-title":"Alzheimer\u2032s Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1002\/alz.12806","article-title":"Differences between blood and cerebrospinal fluid glial fibrillary Acidic protein levels: The effect of sample stability","volume":"18","author":"Weninger","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.ajpath.2011.05.047","article-title":"Reactive glia not only associates with plaques but also parallels tangles in Alzheimer\u2019s disease","volume":"179","author":"Mielke","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S1474-4422(18)30231-X","article-title":"Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): A multicentre observational study","volume":"17","author":"Bazarian","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Abdelhak, A., Hottenrott, T., Morenas-Rodr\u00edguez, E., Su\u00e1rez-Calvet, M., Zettl, U.K., Haass, C., Meuth, S.G., Rauer, S., Otto, M., and Tumani, H. (2019). Glial Activation Markers in CSF and Serum From Patients With Primary Progressive Multiple Sclerosis: Potential of Serum GFAP as Disease Severity Marker?. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00280"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120248","DOI":"10.1016\/j.cca.2025.120248","article-title":"The value of serum glial fibrillary acidic protein as a biomarker of astrogliosis in different neurological diseases","volume":"572","author":"Agnello","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100038","DOI":"10.1016\/j.neumar.2025.100038","article-title":"Glial fibrillary acidic protein as a biomarker for diagnosis of Alzheimer\u2019s disease in cerebrospinal fluid, plasma and saliva measured with Lumipulse technology: A narrative review","volume":"2","author":"Marksteiner","year":"2025","journal-title":"NeuroMarkers"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","article-title":"Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses","volume":"41","author":"Faul","year":"2009","journal-title":"Behav. Res. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.clinbiochem.2016.08.003","article-title":"Evaluation of Lumipulse\u00ae G1200 for the measurement of six tumor markers: Comparison with AIA\u00ae 2000","volume":"49","author":"Oudart","year":"2016","journal-title":"Clin. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/alz.12372","article-title":"State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer\u2019s disease","volume":"18","author":"Hampel","year":"2022","journal-title":"Alzheimers Dement."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8134\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:41Z","timestamp":1760034821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":28,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178134"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178134","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]}}}