{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:53:59Z","timestamp":1787061239128,"version":"build-2736575974"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["F31 AG085980"],"award-info":[{"award-number":["F31 AG085980"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24 AG074855"],"award-info":[{"award-number":["U24 AG074855"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24 AG074855"],"award-info":[{"award-number":["U24 AG074855"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG22018"],"award-info":[{"award-number":["R01 AG22018"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG22018"],"award-info":[{"award-number":["R01 AG22018"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24 AG074855"],"award-info":[{"award-number":["U24 AG074855"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24 AG074855"],"award-info":[{"award-number":["U24 AG074855"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Plasma glial fibrillary acidic protein (GFAP) is an emerging biomarker of Alzheimer\u2019s disease (AD), with higher blood GFAP levels linked to faster cognitive decline, particularly among individuals with high brain amyloid burden. However, few studies have examined brain GFAP expression to clarify if peripheral associations reflect brain changes. This study aimed to correlate region-specific GFAP mRNA expression (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a0917) and protein abundance (n=386) with diverse neuropathological measures at autopsy in the Religious Orders Study and Rush Memory and Aging Project (ROS\/MAP) and to characterize the interaction between brain GFAP and brain amyloid burden on downstream outcomes. We assessed GFAP gene expression in the dorsolateral prefrontal cortex, caudate nucleus, and posterior cingulate cortex with respect to core AD pathology (amyloid-\u03b2 and tau), cerebrovascular (microinfarcts, macroinfarcts, and cerebral amyloid angiopathy [CAA]), proteinopathic (TDP-43, Lewy bodies), and cognitive outcomes. These associations were further examined at the protein level using tandem-mass tag proteomic measurements from the dorsolateral prefrontal cortex. We also assessed GFAP interactions with AD neuropathology on downstream outcomes. Cortical GFAP gene and protein expression were significantly upregulated in participants with a neuropathologically confirmed AD diagnosis at autopsy (all P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u00a0&lt;\u00a03.5e\u22124), but not in individuals positive for tau pathology and negative for amyloid pathology (all P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u00a0&gt;\u00a00.05). Higher cortical GFAP levels were associated with increased amyloid pathology, CAA pathology, and faster cognitive decline (all P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u00a0&lt;\u00a03.3e\u22123). GFAP\u2019s associations with phosphorylated tau burden and cognition were influenced by amyloid burden, being most pronounced among amyloid-positive individuals, confirming previous in vivo biomarker observations. No associations were observed between\n                    <jats:italic>GFAP<\/jats:italic>\n                    gene expression and outcomes in the caudate nucleus. Our results support previous biomarker findings and suggest that higher brain GFAP levels are associated with higher brain amyloid burden and faster cognitive decline among amyloid-positive individuals.\n                  <\/jats:p>","DOI":"10.1007\/s00401-024-02828-5","type":"journal-article","created":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T03:44:45Z","timestamp":1732419885000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Pathologic and clinical correlates of region-specific brain GFAP in Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"148","author":[{"given":"Jared M.","family":"Phillips","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Winfree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabel","family":"Seto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan C.","family":"Dumitrescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Hohman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"2828_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12492","volume":"15","author":"M Ally","year":"2023","unstructured":"Ally M, Sugarman MA, Zetterberg H, Blennow K, Ashton NJ, Karikari TK et al (2023) Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer\u2019s disease. Alzheimers Dement 15:e12492. https:\/\/doi.org\/10.1002\/dad2.12492","journal-title":"Alzheimers Dement"},{"key":"2828_CR2","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1161\/STROKEAHA.110.595082","volume":"42","author":"Z Arvanitakis","year":"2011","unstructured":"Arvanitakis Z, Leurgans SE, Barnes LL, Bennett DA, Schneider JA (2011) Microinfarct pathology, dementia, and cognitive systems. Stroke 42:722\u2013727. https:\/\/doi.org\/10.1161\/STROKEAHA.110.595082","journal-title":"Stroke"},{"key":"2828_CR3","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1038\/s41591-023-02380-x","volume":"29","author":"B Bellaver","year":"2023","unstructured":"Bellaver B, Povala G, Ferreira PCL, Ferrari-Souza JP, Leffa DT, Lussier FZ et al (2023) Astrocyte reactivity influences amyloid-\u03b2 effects on tau pathology in preclinical Alzheimer\u2019s disease. Nat Med 29:1775\u20131781. https:\/\/doi.org\/10.1038\/s41591-023-02380-x","journal-title":"Nat Med"},{"key":"2828_CR4","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1001\/jamaneurol.2021.3671","volume":"78","author":"AL Benedet","year":"2021","unstructured":"Benedet AL, Mil\u00e0-Alom\u00e0 M, Vrillon A, Ashton NJ, Pascoal TA, Lussier F et al (2021) Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum. JAMA Neurol 78:1471. https:\/\/doi.org\/10.1001\/jamaneurol.2021.3671","journal-title":"JAMA Neurol"},{"key":"2828_CR5","doi-asserted-by":"publisher","first-page":"646","DOI":"10.2174\/156720512801322663","volume":"9","author":"DA Bennett","year":"2012","unstructured":"Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA, Wilson RS (2012) Overview and Findings from the rush memory and aging project. Curr Alzheimer Res 9:646\u2013663. https:\/\/doi.org\/10.2174\/156720512801322663","journal-title":"Curr Alzheimer Res"},{"key":"2828_CR6","doi-asserted-by":"publisher","first-page":"S397","DOI":"10.3233\/JAD-2012-129007","volume":"33","author":"DA Bennett","year":"2012","unstructured":"Bennett DA, Wilson RS, Arvanitakis Z, Boyle PA, De Toledo-Morrell L, Schneider JA (2012) Selected findings from the religious orders study and rush memory and aging project. JAD 33:S397\u2013S403. https:\/\/doi.org\/10.3233\/JAD-2012-129007","journal-title":"JAD"},{"key":"2828_CR7","doi-asserted-by":"publisher","first-page":"S161","DOI":"10.3233\/JAD-179939","volume":"64","author":"DA Bennett","year":"2018","unstructured":"Bennett DA, Buchman AS, Boyle PA, Barnes LL, Wilson RS, Schneider JA (2018) Religious orders study and rush memory and aging project. J Alzheimers Dis 64:S161\u2013S189. https:\/\/doi.org\/10.3233\/JAD-179939","journal-title":"J Alzheimers Dis"},{"key":"2828_CR8","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1006\/nbdi.2000.0321","volume":"7","author":"I Blasko","year":"2000","unstructured":"Blasko I, Veerhuis R, Stampfer-Kountchev M, Saurwein-Teissl M, Eikelenboom P, Grubeck-Loebenstein B (2000) Costimulatory effects of interferon-\u03b3 and interleukin-1\u03b2 or tumor necrosis factor \u03b1 on the synthesis of A\u03b21-40 and A\u03b21-42 by human astrocytes. Neurobiology of Disease 7:682\u2013689. https:\/\/doi.org\/10.1006\/nbdi.2000.0321","journal-title":"Neurobiology of Disease"},{"key":"2828_CR9","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1212\/WNL.0000000000002175","volume":"85","author":"PA Boyle","year":"2015","unstructured":"Boyle PA, Yu L, Nag S, Leurgans S, Wilson RS, Bennett DA et al (2015) Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons. Neurology 85:1930\u20131936. https:\/\/doi.org\/10.1212\/WNL.0000000000002175","journal-title":"Neurology"},{"key":"2828_CR10","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s40478-018-0606-1","volume":"6","author":"K Ceyz\u00e9riat","year":"2018","unstructured":"Ceyz\u00e9riat K, Ben Haim L, Denizot A, Pommier D, Matos M, Guillemaud O et al (2018) Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer\u2019s disease. Acta Neuropathol Commun 6:104. https:\/\/doi.org\/10.1186\/s40478-018-0606-1","journal-title":"Acta Neuropathol Commun"},{"key":"2828_CR11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41398-020-01137-1","volume":"11","author":"P Chatterjee","year":"2021","unstructured":"Chatterjee P, Pedrini S, Stoops E, Goozee K, Villemagne VL, Asih PR et al (2021) Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer\u2019s disease. Transl Psychiatry 11:27. https:\/\/doi.org\/10.1038\/s41398-020-01137-1","journal-title":"Transl Psychiatry"},{"key":"2828_CR12","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1002\/acn3.51768","volume":"10","author":"KAQ Cousins","year":"2023","unstructured":"Cousins KAQ, Irwin DJ, Chen-Plotkin A, Shaw LM, Arezoumandan S, Lee EB et al (2023) Plasma GFAP associates with secondary Alzheimer\u2019s pathology in Lewy body disease. Ann Clin Transl Neurol 10:802\u2013813. https:\/\/doi.org\/10.1002\/acn3.51768","journal-title":"Ann Clin Transl Neurol"},{"key":"2828_CR13","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s40478-023-01624-8","volume":"11","author":"DL Dai","year":"2023","unstructured":"Dai DL, Li M, Lee EB (2023) Human Alzheimer\u2019s disease reactive astrocytes exhibit a loss of homeostastic gene expression. Acta Neuropathol Commun 11:127. https:\/\/doi.org\/10.1186\/s40478-023-01624-8","journal-title":"Acta Neuropathol Commun"},{"key":"2828_CR14","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/ana.26817","volume":"95","author":"HE Dark","year":"2024","unstructured":"Dark HE, Paterson C, Daya GN, Peng Z, Duggan MR, Bilgel M et al (2024) Proteomic indicators of health predict Alzheimer\u2019s disease biomarker levels and dementia risk. Ann Neurol 95:260\u2013273. https:\/\/doi.org\/10.1002\/ana.26817","journal-title":"Ann Neurol"},{"key":"2828_CR15","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","volume":"24","author":"C Escartin","year":"2021","unstructured":"Escartin C, Galea E, Lakatos A, O\u2019Callaghan JP, Petzold GC, Serrano-Pozo A et al (2021) Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci 24:312\u2013325. https:\/\/doi.org\/10.1038\/s41593-020-00783-4","journal-title":"Nat Neurosci"},{"key":"2828_CR16","doi-asserted-by":"publisher","unstructured":"Habib N, Avraham-Davidi I, Basu A, Burks T, Shekhar K, Hofree M, Choudhury SR, Aguet F, Gelfand E, Ardlie K, Weitz DA, Rozenblatt-Rosen O, Zhang F, Regev A (2017) Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat Methods 14:955\u2013958. https:\/\/doi.org\/10.1038\/nmeth.4407","DOI":"10.1038\/nmeth.4407"},{"key":"2828_CR17","doi-asserted-by":"publisher","first-page":"1375302","DOI":"10.3389\/fendo.2024.1375302","volume":"15","author":"A Ingannato","year":"2024","unstructured":"Ingannato A, Bagnoli S, Mazzeo S, Giacomucci G, Bessi V, Ferrari C et al (2024) Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia. Front Endocrinol 15:1375302. https:\/\/doi.org\/10.3389\/fendo.2024.1375302","journal-title":"Front Endocrinol"},{"key":"2828_CR18","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41591-020-0815-6","volume":"26","author":"ECB Johnson","year":"2020","unstructured":"Johnson ECB, Dammer EB, Duong DM, Ping L, Zhou M, Yin L et al (2020) Large-scale proteomic analysis of Alzheimer\u2019s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat Med 26:769\u2013780. https:\/\/doi.org\/10.1038\/s41591-020-0815-6","journal-title":"Nat Med"},{"key":"2828_CR19","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/glia.23759","volume":"68","author":"L Katsouri","year":"2020","unstructured":"Katsouri L, Birch AM, Renziehausen AWJ, Zach C, Aman Y, Steeds H et al (2020) Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer\u2019s disease. Glia 68:1017\u20131030. https:\/\/doi.org\/10.1002\/glia.23759","journal-title":"Glia"},{"key":"2828_CR20","doi-asserted-by":"publisher","first-page":"676","DOI":"10.3390\/cells10030676","volume":"10","author":"J-H Kim","year":"2021","unstructured":"Kim J-H, Rahman MH, Park D, Jo M, Kim H-J, Suk K (2021) Identification of genetic modifiers of TDP-43: inflammatory activation of astrocytes for neuroinflammation. Cells 10:676. https:\/\/doi.org\/10.3390\/cells10030676","journal-title":"Cells"},{"key":"2828_CR21","doi-asserted-by":"publisher","first-page":"8240","DOI":"10.1523\/JNEUROSCI.1808-05.2005","volume":"25","author":"J Koenigsknecht-Talboo","year":"2005","unstructured":"Koenigsknecht-Talboo J, Landreth GE (2005) Microglial phagocytosis induced by Fibrillar \u03b2-Amyloid and IgGs are differentially regulated by proinflammatory cytokines. J Neurosci 25:8240\u20138249. https:\/\/doi.org\/10.1523\/JNEUROSCI.1808-05.2005","journal-title":"J Neurosci"},{"key":"2828_CR22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neulet.2009.11.034","volume":"469","author":"AO Koob","year":"2010","unstructured":"Koob AO, Paulino AD, Masliah E (2010) GFAP reactivity, apolipoprotein E redistribution and cholesterol reduction in human astrocytes treated with \u03b1-synuclein. Neurosci Lett 469:11\u201314. https:\/\/doi.org\/10.1016\/j.neulet.2009.11.034","journal-title":"Neurosci Lett"},{"key":"2828_CR23","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1096\/fj.12-208660","volume":"27","author":"AW Kraft","year":"2013","unstructured":"Kraft AW, Hu X, Yoon H, Yan P, Xiao Q, Wang Y et al (2013) Attenuating astrocyte activation accelerates plaque pathogenesis in APP\/PS1 mice. FASEB j 27:187\u2013198. https:\/\/doi.org\/10.1096\/fj.12-208660","journal-title":"FASEB j"},{"key":"2828_CR24","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481\u2013487. https:\/\/doi.org\/10.1038\/nature21029","journal-title":"Nature"},{"key":"2828_CR25","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041356","author":"SA Liddelow","year":"2024","unstructured":"Liddelow SA, Olsen ML, Sofroniew MV (2024) Reactive astrocytes and emerging roles in central nervous system (CNS) disorders. Cold Spring Harb Perspect Biol. https:\/\/doi.org\/10.1101\/cshperspect.a041356","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2828_CR26","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1186\/1742-2094-10-90","volume":"10","author":"A Marutle","year":"2013","unstructured":"Marutle A, Gillberg P-G, Bergfors A, Yu W, Ni R, Nennesmo I et al (2013) 3H-Deprenyl and 3H-PIB autoradiography show different laminar distributions of astroglia and fibrillar \u03b2-amyloid in Alzheimer brain. J Neuroinflammation 10:861. https:\/\/doi.org\/10.1186\/1742-2094-10-90","journal-title":"J Neuroinflammation"},{"key":"2828_CR27","doi-asserted-by":"publisher","unstructured":"Mathys H, Davila-Velderrain J, Peng Z, Gao F, Mohammadi S, Young JZ, Menon M, He L, Abdurrob F, Jiang X, Martorell AJ, Ransohoff RM, Hafler BP, Bennett DA, Kellis M, Tsai L-H (2019) Single-cell transcriptomic analysis of Alzheimer\u2019s disease. Nature 570:332\u2013337. https:\/\/doi.org\/10.1038\/s41586-019-1195-2","DOI":"10.1038\/s41586-019-1195-2"},{"key":"2828_CR28","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s40478-018-0531-3","volume":"6","author":"S Nag","year":"2018","unstructured":"Nag S, Yu L, Boyle PA, Leurgans SE, Bennett DA, Schneider JA (2018) TDP-43 pathology in anterior temporal pole cortex in aging and Alzheimer\u2019s disease. Acta Neuropathol Commun 6:33. https:\/\/doi.org\/10.1186\/s40478-018-0531-3","journal-title":"Acta Neuropathol Commun"},{"key":"2828_CR29","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3389\/fnana.2020.00031","volume":"14","author":"LA O\u2019Leary","year":"2020","unstructured":"O\u2019Leary LA, Davoli MA, Belliveau C, Tanti A, Ma JC, Farmer WT et al (2020) Characterization of vimentin-immunoreactive astrocytes in the human brain. Front Neuroanat 14:31. https:\/\/doi.org\/10.3389\/fnana.2020.00031","journal-title":"Front Neuroanat"},{"key":"2828_CR30","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005677","author":"S Oveisgharan","year":"2018","unstructured":"Oveisgharan S, Buchman AS, Yu L, Farfel J, Hachinski V, Gaiteri C et al (2018) APOE \u03b52\u03b54 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults. Neurology. https:\/\/doi.org\/10.1212\/WNL.0000000000005677","journal-title":"Neurology"},{"key":"2828_CR31","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3233\/ADR-230029","volume":"7","author":"MV Pais","year":"2023","unstructured":"Pais MV, Forlenza OV, Diniz BS (2023) Plasma biomarkers of Alzheimer\u2019s disease: a review of available assays, recent developments, and implications for clinical practice. J Alzheimer\u2019s Dis Rep 7:355\u2013380. https:\/\/doi.org\/10.3233\/ADR-230029","journal-title":"J Alzheimer\u2019s Dis Rep"},{"key":"2828_CR32","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s40478-021-01180-z","volume":"9","author":"J-S Park","year":"2021","unstructured":"Park J-S, Kam T-I, Lee S, Park H, Oh Y, Kwon S-H et al (2021) Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer\u2019s disease. Acta Neuropathol Commun 9:78. https:\/\/doi.org\/10.1186\/s40478-021-01180-z","journal-title":"Acta Neuropathol Commun"},{"key":"2828_CR33","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1093\/brain\/awab223","volume":"144","author":"JB Pereira","year":"2021","unstructured":"Pereira JB, Janelidze S, Smith R, Mattsson-Carlgren N, Palmqvist S, Teunissen CE et al (2021) Plasma GFAP is an early marker of amyloid-\u03b2 but not tau pathology in Alzheimer\u2019s disease. Brain 144:3505\u20133516. https:\/\/doi.org\/10.1093\/brain\/awab223","journal-title":"Brain"},{"key":"2828_CR34","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.3889\/oamjms.2019.326","volume":"7","author":"V Puspitasari","year":"2019","unstructured":"Puspitasari V, Gunawan PY, Wiradarma HD, Hartoyo V (2019) Glial fibrillary acidic protein serum level as a predictor of clinical outcome in ischemic stroke. Open Access Maced J Med Sci 7:1471\u20131474. https:\/\/doi.org\/10.3889\/oamjms.2019.326","journal-title":"Open Access Maced J Med Sci"},{"key":"2828_CR35","doi-asserted-by":"publisher","first-page":"13630","DOI":"10.3390\/ijms232113630","volume":"23","author":"M Rodr\u00edguez-Giraldo","year":"2022","unstructured":"Rodr\u00edguez-Giraldo M, Gonz\u00e1lez-Reyes RE, Ram\u00edrez-Guerrero S, Bonilla-Trilleras CE, Guardo-Maya S, Nava-Mesa MO (2022) Astrocytes as a therapeutic target in Alzheimer\u2019s disease-comprehensive review and recent developments. IJMS 23:13630. https:\/\/doi.org\/10.3390\/ijms232113630","journal-title":"IJMS"},{"key":"2828_CR36","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202217123","volume":"15","author":"G Salvad\u00f3","year":"2023","unstructured":"Salvad\u00f3 G, Ossenkoppele R, Ashton NJ, Beach TG, Serrano GE, Reiman EM et al (2023) Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads. EMBO Mol Med 15:e17123. https:\/\/doi.org\/10.15252\/emmm.202217123","journal-title":"EMBO Mol Med"},{"key":"2828_CR37","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1093\/brain\/awae035","volume":"147","author":"P S\u00e1nchez-Juan","year":"2024","unstructured":"S\u00e1nchez-Juan P, Valeriano-Lorenzo E, Ruiz-Gonz\u00e1lez A, Pastor AB, Rodrigo Lara H, L\u00f3pez-Gonz\u00e1lez F et al (2024) Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles. Brain 147:1667\u20131679. https:\/\/doi.org\/10.1093\/brain\/awae035","journal-title":"Brain"},{"key":"2828_CR38","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1161\/01.STR.0000160747.27470.2a","volume":"36","author":"JA Schneider","year":"2005","unstructured":"Schneider JA, Bienias JL, Wilson RS, Berry-Kravis E, Evans DA, Bennett DA (2005) The apolipoprotein E \u03b54 allele increases the odds of chronic cerebral infarction detected at autopsy in older persons. Stroke 36:954\u2013959. https:\/\/doi.org\/10.1161\/01.STR.0000160747.27470.2a","journal-title":"Stroke"},{"key":"2828_CR39","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1093\/brain\/aws234","volume":"135","author":"JA Schneider","year":"2012","unstructured":"Schneider JA, Arvanitakis Z, Yu L, Boyle PA, Leurgans SE, Bennett DA (2012) Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain 135:3005\u20133014. https:\/\/doi.org\/10.1093\/brain\/aws234","journal-title":"Brain"},{"key":"2828_CR40","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/j.ajpath.2011.05.047","volume":"179","author":"A Serrano-Pozo","year":"2011","unstructured":"Serrano-Pozo A, Mielke ML, G\u00f3mez-Isla T, Betensky RA, Growdon JH, Frosch MP et al (2011) Reactive glia not only associates with plaques but also parallels tangles in Alzheimer\u2019s disease. Am J Pathol 179:1373\u20131384. https:\/\/doi.org\/10.1016\/j.ajpath.2011.05.047","journal-title":"Am J Pathol"},{"key":"2828_CR41","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.neurobiolaging.2022.06.011","volume":"118","author":"M Seto","year":"2022","unstructured":"Seto M, Weiner RL, Dumitrescu L, Mahoney ER, Hansen SL, Janve V et al (2022) RNASE6 is a novel modifier of APOE-\u03b54 effects on cognition. Neurobiol Aging 118:66\u201376. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2022.06.011","journal-title":"Neurobiol Aging"},{"key":"2828_CR42","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.755955","volume":"15","author":"X-Y Shen","year":"2021","unstructured":"Shen X-Y, Gao Z-K, Han Y, Yuan M, Guo Y-S, Bi X (2021) Activation and role of astrocytes in ischemic stroke. Front Cell Neurosci 15:755955. https:\/\/doi.org\/10.3389\/fncel.2021.755955","journal-title":"Front Cell Neurosci"},{"key":"2828_CR43","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12291","volume":"14","author":"D Shir","year":"2022","unstructured":"Shir D, Graff-Radford J, Hofrenning EI, Lesnick TG, Przybelski SA, Lowe VJ et al (2022) Association of plasma glial fibrillary acidic protein (GFAP) with neuroimaging of Alzheimer\u2019s disease and vascular pathology. Alzheimers Dement 14:e12291. https:\/\/doi.org\/10.1002\/dad2.12291","journal-title":"Alzheimers Dement"},{"key":"2828_CR44","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1093\/brain\/awz419","volume":"143","author":"P Smethurst","year":"2020","unstructured":"Smethurst P, Risse E, Tyzack GE, Mitchell JS, Taha DM, Chen Y-R et al (2020) Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis. Brain 143:430\u2013440. https:\/\/doi.org\/10.1093\/brain\/awz419","journal-title":"Brain"},{"key":"2828_CR45","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020420","volume":"7","author":"MV Sofroniew","year":"2015","unstructured":"Sofroniew MV (2015) Astrogliosis. Cold Spring Harb Perspect Biol 7:a020420. https:\/\/doi.org\/10.1101\/cshperspect.a020420","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2828_CR46","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.it.2020.07.004","volume":"41","author":"MV Sofroniew","year":"2020","unstructured":"Sofroniew MV (2020) Astrocyte reactivity: subtypes, states, and functions in CNS innate immunity. Trends Immunol 41:758\u2013770. https:\/\/doi.org\/10.1016\/j.it.2020.07.004","journal-title":"Trends Immunol"},{"key":"2828_CR47","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","volume":"58","author":"DR Thal","year":"2002","unstructured":"Thal DR, R\u00fcb U, Orantes M, Braak H (2002) Phases of A\u03b2-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791\u20131800. https:\/\/doi.org\/10.1212\/WNL.58.12.1791","journal-title":"Neurology"},{"key":"2828_CR48","doi-asserted-by":"publisher","first-page":"e87","DOI":"10.1016\/S2666-7568(20)30061-1","volume":"2","author":"IMW Verberk","year":"2021","unstructured":"Verberk IMW, Laarhuis MB, Van Den Bosch KA, Ebenau JL, Van Leeuwenstijn M, Prins ND et al (2021) Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic-based cohort study. Lancet Healthy Longev 2:e87\u2013e95. https:\/\/doi.org\/10.1016\/S2666-7568(20)30061-1","journal-title":"Lancet Healthy Longev"},{"key":"2828_CR49","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12916-024-03418-8","volume":"22","author":"X Wang","year":"2024","unstructured":"Wang X, Shi Z, Qiu Y, Sun D, Zhou H (2024) Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank. BMC Med 22:192. https:\/\/doi.org\/10.1186\/s12916-024-03418-8","journal-title":"BMC Med"},{"key":"2828_CR50","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s00401-023-02564-2","volume":"145","author":"RL Winfree","year":"2023","unstructured":"Winfree RL, Seto M, Dumitrescu L, Menon V, De Jager P, Wang Y et al (2023) TREM2 gene expression associations with Alzheimer\u2019s disease neuropathology are region-specific: implications for cortical versus subcortical microglia. Acta Neuropathol 145:733\u2013747. https:\/\/doi.org\/10.1007\/s00401-023-02564-2","journal-title":"Acta Neuropathol"},{"key":"2828_CR51","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1111\/j.1468-1331.2006.01435.x","volume":"13","author":"MT Wunderlich","year":"2006","unstructured":"Wunderlich MT, Wallesch CW, Goertler M (2006) Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Eur J Neurol 13:1118\u20131123. https:\/\/doi.org\/10.1111\/j.1468-1331.2006.01435.x","journal-title":"Eur J Neurol"},{"key":"2828_CR52","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.tins.2015.04.003","volume":"38","author":"Z Yang","year":"2015","unstructured":"Yang Z, Wang KKW (2015) Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 38:364\u2013374. https:\/\/doi.org\/10.1016\/j.tins.2015.04.003","journal-title":"Trends Neurosci"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-024-02828-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-024-02828-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-024-02828-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T04:02:18Z","timestamp":1732420938000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-024-02828-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,24]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2828"],"URL":"https:\/\/doi.org\/10.1007\/s00401-024-02828-5","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,24]]},"assertion":[{"value":"26 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study adhered to the principles outlined in the Declaration of Helsinki. All protocols received approval from the Rush University Medical Center Institutional Review Board, and written informed consent, including the Anatomical Gift Act, was obtained from all participants. The secondary analyses were approved by the Vanderbilt University Medical Center Institutional Review Board under protocol number 170135.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"All authors have given consent to the publication of this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"69"}}