{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:22:02Z","timestamp":1791573722219,"version":"4.3.4"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Queen Sofia"},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer\u2019s disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology.<\/jats:p>\n                  <jats:p>In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-frame between GFAP level determination and neuropathological assessment was exceptionally short (on average 139\u2005days), we analysed this biomarker, measured at three time points, in relation to proxies of disease progression such as cognitive decline and brain weight. Most importantly, we investigated the use of blood GFAP to detect the neuropathological hallmarks of Alzheimer\u2019s disease, while accounting for potential influences of the most frequent brain co-pathologies.<\/jats:p>\n                  <jats:p>The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (\u03b2 = 12.85; P &amp;lt; 0.001) that was independent of amyloid deposits (\u03b2 = 13.23; P = 0.02). A mediation analysis provided additional support for the role of astrocytic activation as a link between amyloid and tau pathology in Alzheimer\u2019s disease. Furthermore, a negative correlation was observed between pre-mortem serum GFAP and brain weight at post-mortem (r = \u22120.35; P &amp;lt; 0.001). This finding, together with evidence of a negative correlation with cognitive assessments (r = \u22120.27; P = 0.005), supports the role of GFAP as a biomarker for disease monitoring, even in the late phases of Alzheimer\u2019s disease.<\/jats:p>\n                  <jats:p>Moreover, the diagnostic performance of GFAP in advanced dementia patients was explored, and its discriminative power (area under the receiver operator characteristic curve at baseline = 0.91) in differentiating neuropathologically-confirmed Alzheimer\u2019s disease dementias from non-Alzheimer\u2019s disease dementias was determined, despite the challenging scenario of advanced age and frequent co-pathologies in these patients. Independently of Alzheimer\u2019s disease, serum GFAP levels were shown to be associated with two other pathologies targeting the temporal lobes\u2014hippocampal sclerosis (\u03b2 = 3.64; P = 0.03) and argyrophilic grain disease (\u03b2 = \u22126.11; P = 0.02).<\/jats:p>\n                  <jats:p>Finally, serum GFAP levels were revealed to be correlated with astrocyte reactivity, using the brain GFAP-immunostained area as a proxy (\u03c1 = 0.21; P = 0.02).<\/jats:p>\n                  <jats:p>Our results contribute to increasing evidence suggesting a role for blood GFAP as an Alzheimer\u2019s disease biomarker, and the findings offer mechanistic insights into the relationship between blood GFAP and Alzheimer\u2019s disease neuropathology, highlighting its ties with tau burden. Moreover, the data highlighting an independent association between serum GFAP levels and other neuropathological lesions provide information for clinicians to consider when interpreting test results.<\/jats:p>\n                  <jats:p>The longitudinal design and correlation with post-mortem data reinforce the robustness of our findings. However, studies correlating blood biomarkers and neuropathological assessments are still scant, and further research is needed to replicate and validate these results in diverse populations.<\/jats:p>","DOI":"10.1093\/brain\/awae035","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T07:50:59Z","timestamp":1706773859000},"page":"1667-1679","source":"Crossref","is-referenced-by-count":96,"title":["Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-8037","authenticated-orcid":false,"given":"Pascual","family":"S\u00e1nchez-Juan","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"},{"name":"CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Valeriano-Lorenzo","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Ruiz-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Bel\u00e9n","family":"Pastor","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Rodrigo Lara","sequence":"additional","affiliation":[{"name":"Banco de Cerebros de la Regi\u00f3n de Murcia , Neuropathology Department, 30120 Murcia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"L\u00f3pez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Ascensi\u00f3n","family":"Zea-Sevilla","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Valent\u00ed","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research Platforms, 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belen","family":"Frades","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Centre Reina Sofia-CIEN Foundation-ISCIII , Research 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