{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:26:36Z","timestamp":1788024396948,"version":"build-2784847793"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"13","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010434","name":"\u201cla Caixa\u201d Foundation","doi-asserted-by":"publisher","award":["LCF\/PR\/GN17\/50300004"],"award-info":[{"award-number":["LCF\/PR\/GN17\/50300004"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005163","name":"Tribeca Film Institute","doi-asserted-by":"publisher","award":["TriBEKa-17-519007"],"award-info":[{"award-number":["TriBEKa-17-519007"]}],"id":[{"id":"10.13039\/100005163","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universities and Research Secretariat","award":["2017-SGR-892"],"award-info":[{"award-number":["2017-SGR-892"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["RYC-2013-13054"],"award-info":[{"award-number":["RYC-2013-13054"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00155"],"award-info":[{"award-number":["PI19\/00155"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["IJC2018-037478-I"],"award-info":[{"award-number":["IJC2018-037478-I"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eurofingers","award":["733051102"],"award-info":[{"award-number":["733051102"]}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2018-02532"],"award-info":[{"award-number":["2018-02532"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Research Council","award":["681712"],"award-info":[{"award-number":["681712"]}]},{"name":"Swedish State Support for Clinical Research","award":["ALFGBG-720931"],"award-info":[{"award-number":["ALFGBG-720931"]}]},{"DOI":"10.13039\/100002565","name":"Alzheimer's Drug Discovery Foundation","doi-asserted-by":"publisher","award":["201809-2016862"],"award-info":[{"award-number":["201809-2016862"]}],"id":[{"id":"10.13039\/100002565","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AD strategic fund","award":["ADSF-21-831376-C"],"award-info":[{"award-number":["ADSF-21-831376-C"]}]},{"name":"AD strategic fund","award":["ADSF-21-831381-C"],"award-info":[{"award-number":["ADSF-21-831381-C"]}]},{"name":"AD strategic fund","award":["ADSF-21-831377-C"],"award-info":[{"award-number":["ADSF-21-831377-C"]}]},{"name":"Olay Thon Fundation","award":["FO2019-0228"],"award-info":[{"award-number":["FO2019-0228"]}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["860197"],"award-info":[{"award-number":["860197"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"crossref","award":["2017-00915"],"award-info":[{"award-number":["2017-00915"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Alzheimer Foundation","award":["AF-742881"],"award-info":[{"award-number":["AF-742881"]}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","award":["FO2017-0243"],"award-info":[{"award-number":["FO2017-0243"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012558","name":"Sk\u00e5ne County Council's Research and Development Foundation","doi-asserted-by":"publisher","award":["ALFGBG-715986"],"award-info":[{"award-number":["ALFGBG-715986"]}],"id":[{"id":"10.13039\/100012558","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["JPND2019-466-236"],"award-info":[{"award-number":["JPND2019-466-236"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AG068398-01"],"award-info":[{"award-number":["1R01AG068398-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Glial activation is one of the earliest mechanisms to be altered in Alzheimer\u2019s disease (AD). Glial fibrillary acidic protein (GFAP) relates to reactive astrogliosis and can be measured in both cerebrospinal fluid (CSF) and blood. Plasma GFAP has been suggested to become altered earlier in AD than its CSF counterpart. Although astrocytes consume approximately half of the glucose-derived energy in the brain, the relationship between reactive astrogliosis and cerebral glucose metabolism is poorly understood. Here, we aimed to investigate the association between fluorodeoxyglucose ([\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG) uptake and reactive astrogliosis, by means of GFAP quantified in both plasma and CSF for the same participants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included 314 cognitively unimpaired participants from the ALFA\u2009+\u2009cohort, 112 of whom were amyloid-\u03b2 (A\u03b2) positive. Associations between GFAP markers and [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG uptake were studied. We also investigated whether these associations were modified by A\u03b2 and tau status (AT stages).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma GFAP was positively associated with glucose consumption in the whole brain, while CSF GFAP associations with [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG uptake were only observed in specific smaller areas like temporal pole and superior temporal lobe. These associations persisted when accounting for biomarkers of A\u03b2 pathology but became negative in A\u03b2-positive and tau-positive participants (A\u2009+\u2009T\u2009+) in similar areas of AD-related hypometabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher astrocytic reactivity, probably in response to early AD pathological changes, is related to higher glucose consumption. With the onset of tau pathology, the observed uncoupling between astrocytic biomarkers and glucose consumption might be indicative of a failure to sustain the higher energetic demands required by reactive astrocytes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-022-05897-4","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T01:02:40Z","timestamp":1658106160000},"page":"4567-4579","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer\u2019s continuum"],"prefix":"10.1007","volume":"49","author":[{"given":"Gemma","family":"Salvad\u00f3","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mil\u00e0-Alom\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahnaz","family":"Shekari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Operto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Falcon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Cacciaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Minguillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Fauria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Ni\u00f1erola-Baiz\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Perissinotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a L.","family":"Benedet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendlyn","family":"Kollmorgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Suridjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Wild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Molinuevo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Su\u00e1rez-Calvet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6155-0642","authenticated-orcid":false,"given":"Juan Domingo","family":"Gispert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the ALFA Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"5897_CR1","doi-asserted-by":"crossref","unstructured":"Mil\u00e0-Alom\u00e0 M, Salvad\u00f3 G, Gispert JD, Vilor-Tejedor N, Grau-Rivera O, Sala-Vila A, et al. Amyloid-\u03b2, tau, synaptic, neurodegeneration and glial biomarkers in the preclinical stage of the Alzheimer\u2019s continuum. Alzheimer\u2019s Dement. 2020;1\u201314.","DOI":"10.1002\/alz.12131"},{"key":"5897_CR2","doi-asserted-by":"crossref","unstructured":"Salvad\u00f3 G, Mil\u00e0-Alom\u00e0 M, Shekari M, Minguillon C, Fauria K, Ni\u00f1erola-Baiz\u00e1n A, et al. Cerebral amyloid-\u03b2 load is associated with neurodegeneration and gliosis: mediation by p-tau and interactions with risk factors early in the Alzheimer\u2019s continuum. Alzheimer\u2019s Dement. 2021;1\u201313.","DOI":"10.1002\/alz.12245"},{"key":"5897_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15252\/emmm.201911170","volume":"11","author":"S Palmqvist","year":"2019","unstructured":"Palmqvist S, Insel PS, Stomrud E, Janelidze S, Zetterberg H, Brix B, et al. Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer\u2019s disease. EMBO Mol Med. 2019;11:1\u201313.","journal-title":"EMBO Mol Med"},{"key":"5897_CR4","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.jalz.2019.01.004","volume":"15","author":"I Bos","year":"2019","unstructured":"Bos I, Vos S, Verhey F, Scheltens P, Teunissen C, Engelborghs S, et al. Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer\u2019s disease spectrum. Alzheimer\u2019s Dement. 2019;15:644\u201354.","journal-title":"Alzheimer\u2019s Dement"},{"key":"5897_CR5","doi-asserted-by":"publisher","first-page":"e867","DOI":"10.1212\/WNL.0000000000006082","volume":"91","author":"S Janelidze","year":"2018","unstructured":"Janelidze S, Mattsson N, Stomrud E, Lindberg O, Palmqvist S, Zetterberg H, et al. CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease. Neurology. 2018;91:e867\u201377.","journal-title":"Neurology"},{"key":"5897_CR6","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","volume":"14","author":"MT Heneka","year":"2015","unstructured":"Heneka MT, Carson MJ, el Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer\u2019s disease. The Lancet Neurol. 2015;14:388\u2013405.","journal-title":"The Lancet Neurol"},{"key":"5897_CR7","doi-asserted-by":"crossref","unstructured":"Ewers M, Franzmeier N, Su\u00e1rez-Calvet M, Morenas-Rodriguez E, Caballero MAA, Kleinberger G, et al. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer\u2019s disease. Sci Transl Med. 2019;11.","DOI":"10.1126\/scitranslmed.aav6221"},{"key":"5897_CR8","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1093\/cercor\/bhz240","volume":"30","author":"NB Halaas","year":"2020","unstructured":"Halaas NB, Henjum K, Blennow K, Dakhil S, Idland A-V, Nilsson LN, et al. CSF sTREM2 and tau work together in predicting increased temporal lobe atrophy in older adults. Cereb Cortex United States. 2020;30:2295\u2013306.","journal-title":"Cereb Cortex United States"},{"key":"5897_CR9","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.nurt.2010.05.017","volume":"7","author":"A Verkhratsky","year":"2010","unstructured":"Verkhratsky A, Olabarria M, Noristani HN, Yeh CY, Rodriguez JJ. Astrocytes in Alzheimer\u2019s disease. Neurotherapeutics. Neurotherapeutics. 2010;7:399\u2013412.","journal-title":"Neurotherapeutics"},{"key":"5897_CR10","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. Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci Nat Publ Group. 2021;24:312\u201325.","journal-title":"Nat Neurosci Nat Publ Group"},{"key":"5897_CR11","doi-asserted-by":"crossref","unstructured":"Bellaver B, Ferrari-souza JP, Uglione L, Carter SF, Rodriguez-Vieitez E, Nordberg A, et al. Astrocyte biomarkers in Alzheimer\u2019s disease: a systematic review and meta-analysis. Neurology. 2021;1\u201337.","DOI":"10.1212\/WNL.0000000000012109"},{"key":"5897_CR12","doi-asserted-by":"publisher","first-page":"481","DOI":"10.3233\/JAD-180325","volume":"67","author":"P Oeckl","year":"2019","unstructured":"Oeckl P, Halbgebauer S, Anderl-Straub S, Steinacker P, Huss AM, Neugebauer H, et al. Glial fibrillary acidic protein in serum is increased in Alzheimer\u2019s disease and correlates with cognitive impairment. J Alzheimer\u2019s Dis. 2019;67:481\u20138.","journal-title":"J Alzheimer\u2019s Dis"},{"key":"5897_CR13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s13195-020-00682-7","volume":"12","author":"IMW Verberk","year":"2020","unstructured":"Verberk IMW, Thijssen E, Koelewijn J, Mauroo K, Vanbrabant J, de Wilde A, et al. Combination of plasma amyloid beta(1\u201342\/1\u201340) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimer\u2019s Res Ther. 2020;12:118.","journal-title":"Alzheimer\u2019s Res Ther"},{"key":"5897_CR14","doi-asserted-by":"crossref","unstructured":"Asken BM, Elahi FM, La Joie R, Strom A, Staffaroni AM, Lindbergh CA, et al. Plasma glial fibrillary acidic protein levels differ along the spectra of amyloid burden and clinical disease stage. J Alzheimers Dis. 2020. p. 265\u201376.","DOI":"10.3233\/JAD-200755"},{"key":"5897_CR15","doi-asserted-by":"crossref","unstructured":"Elahi FM, Casaletto KB, La Joie R, Walters SM, Harvey D, Wolf A, et al. Plasma biomarkers of astrocytic and neuronal dysfunction in early\u2010 and late\u2010onset Alzheimer\u2019s disease. Alzheimer\u2019s & Dementia. John Wiley and Sons Inc; 2020;16:681\u201395.","DOI":"10.1016\/j.jalz.2019.09.004"},{"key":"5897_CR16","doi-asserted-by":"crossref","unstructured":"Cicognola C, Janelidze S, Hertze J, Zetterberg H, Blennow K, Mattsson-Carlgren N, et al. Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment. Alzheimer\u2019s Res Ther. BioMed Central Ltd; 2021;13.","DOI":"10.1186\/s13195-021-00804-9"},{"key":"5897_CR17","doi-asserted-by":"crossref","unstructured":"Simr\u00e9n J, Leuzy A, Karikari TK, Hye A, Benedet AL, Lantero-Rodriguez J, et al. The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer\u2019s disease. Alzheimer\u2019s and Dementia. John Wiley and Sons Inc; 2021.","DOI":"10.1002\/alz.12283"},{"key":"5897_CR18","doi-asserted-by":"crossref","unstructured":"Ros\u00e9n C, Mattsson N, Johansson PM, Andreasson U, Wallin A, Hansson O, et al. Discriminatory analysis of biochip-derived protein patterns in CSF and plasma in neurodegenerative diseases. Front Aging Neurosci. Frontiers Media SA; 2011;3:1.","DOI":"10.3389\/fnagi.2011.00001"},{"key":"5897_CR19","doi-asserted-by":"crossref","unstructured":"Andreasen N, Gottfries J, Vanmechelen E, Vanderstichele H, Davidsson P, Blennow K, et al. Evaluation of GSF biomarkers for axonal and neuronal degeneration, gliosis, and \u03b2-amyloid metabolism in Alzheimer\u2019s disease [2]. Journal of Neurology Neuro Psychiatry. BMJ Publishing Group Ltd; 2001. p. 557\u20138.","DOI":"10.1136\/jnnp.71.4.557"},{"key":"5897_CR20","doi-asserted-by":"crossref","unstructured":"Chatterjee P, Pedrini S, Stoops E, Goozee K, Villemagne VL, Asih PR. Plasma glial fi brillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer \u2019s Dis. Translational Psychiatry. Springer US; 2021;1\u201310.","DOI":"10.1038\/s41398-020-01137-1"},{"key":"5897_CR21","doi-asserted-by":"crossref","unstructured":"Pereira JB, Janelidze S, Smith R, Mattsson-carlgren N, Palmqvist S, Teunissen CE, et al. Plasma GFAP is an early marker of amyloid-\u03b2 but not tau pathology in Alzheimer \u2019s Dis. Brain. 2021;1\u201334.","DOI":"10.1093\/brain\/awab223"},{"key":"5897_CR22","doi-asserted-by":"crossref","unstructured":"Benedet AL, Mil\u00e0-Alom\u00e0 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 Neurology. American Medical Association; 2021;","DOI":"10.1001\/jamaneurol.2021.3671"},{"key":"5897_CR23","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12974-020-01813-5","volume":"17","author":"C-H Chen","year":"2020","unstructured":"Chen C-H, Cheng Y-W, Chen Y-F, Tang S-C, Jeng J-S. Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL. J Neuroinflammation. 2020;17:124.","journal-title":"J Neuroinflammation"},{"key":"5897_CR24","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1136\/jnnp-2019-321954","volume":"91","author":"C Heller","year":"2020","unstructured":"Heller C, Foiani MS, Moore K, Convery R, Bocchetta M, Neason M, et al. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2020;91:263\u201370.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"5897_CR25","doi-asserted-by":"crossref","unstructured":"Huebschmann NA, Luoto TM, Karr JE, Berghem K, Blennow K, Zetterberg H, et al. Comparing glial fibrillary acidic protein (GFAP) in serum and plasma following mild traumatic brain injury in older adults. Front Neurol. 2020;11.","DOI":"10.3389\/fneur.2020.01054"},{"key":"5897_CR26","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/j.neurobiolaging.2009.07.002","volume":"32","author":"SM Landau","year":"2011","unstructured":"Landau SM, Harvey D, Madison CM, Koeppe RA, Reiman EM, Foster NL, et al. Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging. 2011;32:1207\u201318.","journal-title":"Neurobiol Aging"},{"key":"5897_CR27","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/S1474-4422(20)30314-8","volume":"19","author":"G Ch\u00e9telat","year":"2020","unstructured":"Ch\u00e9telat G, Arbizu J, Barthel H, Garibotto V, Law I, Morbelli S, et al. Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer\u2019s disease and other dementias. The Lancet Neurol Elsevier Ltd. 2020;19:951\u201362.","journal-title":"The Lancet Neurol Elsevier Ltd"},{"key":"5897_CR28","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimer\u2019s Dement. 2018;14:535\u201362.","journal-title":"Alzheimer\u2019s Dement"},{"key":"5897_CR29","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.neurobiolaging.2013.09.028","volume":"35","author":"SC Johnson","year":"2014","unstructured":"Johnson SC, Christian BT, Okonkwo OC, Oh JM, Harding S, Xu G, et al. Amyloid burden and neural function in people at risk for Alzheimer\u2019s disease. Neurobiology of Aging. 2014;35:576\u201384. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.09.028.","journal-title":"Neurobiology of Aging"},{"key":"5897_CR30","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1002\/hbm.22173","volume":"35","author":"H Oh","year":"2014","unstructured":"Oh H, Habeck C, Madison C, Jagust W. Covarying alterations in A\u03b2 deposition, glucose metabolism, and gray matter volume in cognitively normal elderly. Hum Brain Mapp. 2014;35:297\u2013308.","journal-title":"Hum Brain Mapp"},{"key":"5897_CR31","doi-asserted-by":"crossref","unstructured":"Salvad\u00f3 G, Shekari M, Falcon C, Operto G, Mil\u00e0-Alom\u00e0 M, S\u00e1nchez-Benavides G, et al. Brain alterations in the early Alzheimer\u2019s continuum with amyloid-\u03b2, tau, glial and neurodegeneration CSF markers. Brain Communications. 2022;4. Available from: https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcac134\/6591150.","DOI":"10.1093\/braincomms\/fcac134"},{"key":"5897_CR32","doi-asserted-by":"publisher","first-page":"E1331","DOI":"10.1212\/WNL.0000000000007133","volume":"92","author":"GD Femminella","year":"2019","unstructured":"Femminella GD, Dani M, Wood M, Fan Z, Calsolaro V, Atkinson R, et al. Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume. Neurology. 2019;92:E1331\u201343.","journal-title":"Neurology"},{"key":"5897_CR33","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.035","volume":"86","author":"PJ Magistretti","year":"2015","unstructured":"Magistretti PJ, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron. 2015;86:883\u2013901. https:\/\/doi.org\/10.1016\/j.neuron.2015.03.035.","journal-title":"Neuron"},{"key":"5897_CR34","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1212\/WNL.0000000000000328","volume":"82","author":"EE Benarroch","year":"2014","unstructured":"Benarroch EE. Brain glucose transporters: implications for neurologic disease. Neurology. 2014;82:1374\u20139.","journal-title":"Neurology"},{"key":"5897_CR35","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1097\/01.WCB.0000128533.84196.D8","volume":"24","author":"A Nehlig","year":"2004","unstructured":"Nehlig A, Wittendorp-Rechenmann E, Lam CD. Selective uptake of [14c]2-deoxyglucose by neurons and astrocytes: high-resolution microautoradiographic imaging by cellular 14C-trajectography combined with immunohistochemistry. J Cereb Blood Flow Metab. 2004;24:1004\u201314.","journal-title":"J Cereb Blood Flow Metab"},{"key":"5897_CR36","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1002\/glia.20376","volume":"55","author":"A Nehlig","year":"2007","unstructured":"Nehlig A, Coles JA. Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes? Glia. 2007;55:1238\u201350.","journal-title":"Glia."},{"key":"5897_CR37","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1111\/j.1460-9568.2010.07584.x","volume":"33","author":"CR Figley","year":"2011","unstructured":"Figley CR, Stroman PW. The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals. Eur J Neurosci. 2011;33:577\u201388.","journal-title":"Eur J Neurosci"},{"key":"5897_CR38","first-page":"445","volume":"1","author":"PJ Magistretti","year":"1996","unstructured":"Magistretti PJ, Pellerin L. The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Mol Psychiatry England. 1996;1:445\u201352.","journal-title":"Mol Psychiatry England"},{"key":"5897_CR39","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nn.4492","volume":"20","author":"ER Zimmer","year":"2017","unstructured":"Zimmer ER, Parent MJ, Souza DG, Leuzy A, Lecrux C, Kim HI, et al. [18F]FDG PET signal is driven by astroglial glutamate transport. Nat Neurosci. 2017;20:393\u20135.","journal-title":"Nat Neurosci"},{"key":"5897_CR40","doi-asserted-by":"crossref","unstructured":"Rocha A, Bellaver B, Souza DG, Schu G, Fontana IC, Venturin GT, et al. Clozapine induces astrocyte-dependent FDG-PET hypometabolism. Eur J Nucl Med Mol Imaging. 2022;","DOI":"10.21203\/rs.3.rs-974963\/v1"},{"key":"5897_CR41","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nn.4513","volume":"20","author":"AJ Stoessl","year":"2017","unstructured":"Stoessl AJ. Glucose utilization: still in the synapse. Nat Neurosci. 2017;20:382\u20134.","journal-title":"Nat Neurosci"},{"key":"5897_CR42","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","volume":"12","author":"V Calsolaro","year":"2016","unstructured":"Calsolaro V, Edison P. Neuroinflammation in Alzheimer\u2019s disease: current evidence and future directions. Alzheimer\u2019s Dement. 2016;12:719\u201332.","journal-title":"Alzheimer\u2019s Dement"},{"key":"5897_CR43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","volume":"17","author":"F Leng","year":"2021","unstructured":"Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17:157\u201372. https:\/\/doi.org\/10.1038\/s41582-020-00435-y.","journal-title":"Nat Rev Neurol"},{"key":"5897_CR44","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","volume":"87","author":"CR Jack","year":"2016","unstructured":"Jack CR, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A\/T\/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87:539\u201347.","journal-title":"Neurology"},{"key":"5897_CR45","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.trci.2016.02.003","volume":"2","author":"JL Molinuevo","year":"2016","unstructured":"Molinuevo JL, Gramunt N, Gispert JD, Fauria K, Esteller M, Minguillon C, et al. The ALFA project: A research platform to identify early pathophysiological features of Alzheimer\u2019s disease. Alzheimer\u2019s Dement: Transl Res Clin Interv. 2016;2:82\u201392.","journal-title":"Alzheimer\u2019s Dement: Transl Res Clin Interv"},{"key":"5897_CR46","unstructured":"Su\u00e1rez-calvet M, Karikari TK, Ashton NJ, Rodr\u00edguez JL, Mil\u00e0-alom\u00e0 M, Gispert JD, et al. Novel tau biomarkers phosphorylated at T 181 , T 217 , or T 231 rise in the initial stages of the preclinical Alzheimer \u2019 s continuum when only subtle changes in A b pathology are detected. EMBO Molecular Medicine. 2020;1\u201319."},{"key":"5897_CR47","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.jalz.2015.09.009","volume":"12","author":"T Bittner","year":"2016","unstructured":"Bittner T, Zetterberg H, Teunissen CE, Ostlund RE, Militello M, Andreasson U, et al. Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of \u03b2-amyloid (1\u201342) in human cerebrospinal fluid. Alzheimer\u2019s Dement. 2016;12:517\u201326. https:\/\/doi.org\/10.1016\/j.jalz.2015.09.009.","journal-title":"Alzheimer\u2019s Dement"},{"key":"5897_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2014.07.003","volume":"11","author":"WE Klunk","year":"2015","unstructured":"Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD, Jagust WJ, et al. The Centiloid project: standardizing quantitative amyloid plaque estimation by PET. Alzheimer\u2019s Dement. 2015;11:1\u201315. https:\/\/doi.org\/10.1016\/j.jalz.2014.07.003.","journal-title":"Alzheimer\u2019s Dement"},{"key":"5897_CR49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13195-018-0453-0","volume":"11","author":"G Salvad\u00f3","year":"2019","unstructured":"Salvad\u00f3 G, Molinuevo JL, Brugulat-Serrat A, Falcon C, Grau-Rivera O, Su\u00e1rez-Calvet M, et al. Centiloid cut-off values for optimal agreement between PET and CSF core AD biomarkers. Alzheimer\u2019s Res Ther. 2019;11:1\u201312.","journal-title":"Alzheimer\u2019s Res Ther"},{"key":"5897_CR50","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S1053-8119(03)00072-7","volume":"19","author":"JD Gispert","year":"2003","unstructured":"Gispert JD, Pascau J, Reig S, Mart\u00ednez-L\u00e1zaro R, Molina V, Garc\u00eda-Barreno P, et al. Influence of the normalization template on the outcome of statistical parametric mapping of PET scans. Neuroimage United States. 2003;19:601\u201312.","journal-title":"Neuroimage United States"},{"key":"5897_CR51","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.bbadis.2011.09.008","volume":"1822","author":"JM Rasmussen","year":"2012","unstructured":"Rasmussen JM, Lakatos A, van Erp TGM, Kruggel F, Keator DB, Fallon JT, et al. Empirical derivation of the reference region for computing diagnostic sensitive 18fluorodeoxyglucose ratios in Alzheimer\u2019s disease based on the ADNI sample. Biochim Biophys Acta. 2012;1822:457\u201366.","journal-title":"Biochim Biophys Acta"},{"key":"5897_CR52","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1111\/j.1745-9125.1998.tb01268.x","volume":"36","author":"R Paternoster","year":"1998","unstructured":"Paternoster R, Brame R, Mazerolle P, Piquero A. Using the correct statistical test for the equality of regression coefficients. Criminology. 1998;36:859\u201366.","journal-title":"Criminology"},{"key":"5897_CR53","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.tins.2013.07.001","volume":"36","author":"P Mergenthaler","year":"2013","unstructured":"Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends in Neurosci Elsevier Ltd. 2013;36:587\u201397.","journal-title":"Trends in Neurosci Elsevier Ltd"},{"key":"5897_CR54","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1515\/hsz-2019-0140","volume":"400","author":"S Zulfiqar","year":"2019","unstructured":"Zulfiqar S, Garg P, Nieweg K. Contribution of astrocytes to metabolic dysfunction in the Alzheimer\u2019s disease brain. Biol Chem Germany. 2019;400:1113\u201327.","journal-title":"Biol Chem Germany"},{"key":"5897_CR55","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neuint.2010.10.013","volume":"58","author":"B Guly\u00e1s","year":"2011","unstructured":"Guly\u00e1s B, Pavlova E, K\u00e1sa P, Gulya K, Bakota L, V\u00e1rszegi S, et al. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-l-deprenyl using whole hemisphere autoradiography. Neurochem Int. 2011;58:60\u20138.","journal-title":"Neurochem Int"},{"key":"5897_CR56","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1093\/brain\/awv404","volume":"139","author":"E Rodriguez-Vieitez","year":"2016","unstructured":"Rodriguez-Vieitez E, Saint-Aubert L, Carter SF, Almkvist O, Farid K, Sch\u00f6ll M, et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer\u2019s disease. Brain. 2016;139:922\u201336.","journal-title":"Brain"},{"key":"5897_CR57","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2967\/jnumed.110.087031","volume":"53","author":"SF Carter","year":"2012","unstructured":"Carter SF, Sch\u00f6ll M, Almkvist O, Wall A, Engler H, L\u00e5ngstr\u00f6m B, et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: A multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012;53:37\u201346.","journal-title":"J Nucl Med"},{"key":"5897_CR58","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/s00259-018-4217-7","volume":"46","author":"SF Carter","year":"2019","unstructured":"Carter SF, Chiotis K, Nordberg A, Rodriguez-Vieitez E. Longitudinal association between astrocyte function and glucose metabolism in autosomal dominant Alzheimer\u2019s disease. European J Nuc Med Mol Imag. 2019;46:348\u201356.","journal-title":"European J Nuc Med Mol Imag"},{"key":"5897_CR59","first-page":"1","volume":"5","author":"M Scholl","year":"2015","unstructured":"Scholl M, Carter SF, Westman E, Rodriguez-Vieitez E, Almkvist O, Thordardottir S, et al. Early astrocytosis in autosomal dominant Alzheimer\u2019s disease measured in vivo by multi-tracer positron emission tomography. Sci Rep Nat Publ Group. 2015;5:1\u201314.","journal-title":"Sci Rep Nat Publ Group"},{"key":"5897_CR60","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41593-020-00764-7","volume":"24","author":"K Leng","year":"2021","unstructured":"Leng K, Li E, Eser R, Piergies A, Sit R, Tan M, et al. Molecular characterization of selectively vulnerable neurons in Alzheimer\u2019s disease. Nat Neurosci. 2021;24:276\u201387.","journal-title":"Nat Neurosci"},{"key":"5897_CR61","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.neurobiolaging.2013.09.028","volume":"35","author":"SC Johnson","year":"2014","unstructured":"Johnson SC, Christian BT, Okonkwo OC, Oh JM, Harding S, Xu G, et al. Amyloid burden and neural function in people at risk for Alzheimer\u2019s Disease. Neurobiol Aging. 2014;35:576\u201384.","journal-title":"Neurobiol Aging"},{"key":"5897_CR62","doi-asserted-by":"crossref","unstructured":"Salvad\u00f3 G, Shekari M, Falcon C, Operto G, Mil\u00e0-Alom\u00e0 M, S\u00e1nchez-Benavides G, et al. Brain alterations in the early Alzheimer\u2019s continuum with amyloid-\u03b2, tau, glial and neurodegeneration CSF markers. Barcelona; 2022.","DOI":"10.1093\/braincomms\/fcac134"},{"key":"5897_CR63","doi-asserted-by":"publisher","first-page":"e1385","DOI":"10.1212\/WNL.0000000000006321","volume":"91","author":"J Gill","year":"2018","unstructured":"Gill J, Latour L, Diaz-Arrastia R, Motamedi V, Turtzo C, Shahim P, et al. Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI. Neurology. 2018;91:e1385\u20139.","journal-title":"Neurology"},{"key":"5897_CR64","doi-asserted-by":"crossref","unstructured":"Frost GR, Li Y-M. The role of astrocytes in amyloid production and Alzheimer\u2019s disease. Open Biol. 2017;7.","DOI":"10.1098\/rsob.170228"},{"key":"5897_CR65","first-page":"9605265","volume":"2019","author":"Z Zhang","year":"2019","unstructured":"Zhang Z, Ma Z, Zou W, Guo H, Liu M, Ma Y, et al. The appropriate marker for astrocytes: comparing the distribution and expression of three astrocytic markers in different mouse cerebral regions. Biomed Res Int. 2019;2019:9605265.","journal-title":"Biomed Res Int"},{"key":"5897_CR66","doi-asserted-by":"crossref","unstructured":"Xiang X, Wind K, Wiedemann T, Blume T, Shi Y, Briel N, et al. Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases [Internet]. Sci. Transl. Med. 2021. Available from: https:\/\/www.science.org","DOI":"10.1126\/scitranslmed.abn5104"},{"key":"5897_CR67","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. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541:481\u20137.","journal-title":"Nature"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-022-05897-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-022-05897-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-022-05897-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T19:05:45Z","timestamp":1667070345000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-022-05897-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,18]]},"references-count":67,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["5897"],"URL":"https:\/\/doi.org\/10.1007\/s00259-022-05897-4","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,18]]},"assertion":[{"value":"10 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ALFA study and the PET sub-study protocols have been approved by an independent Ethics Committee Parc de Salut Mar Barcelona and registered at Clinicaltrials.gov (ALFA Identifier: NCT02485730; PET sub-study Identifier:NCT02685969). Both studies have been conducted in accordance with the directives of the Spanish Law 14\/ 2007, of 3rd of July, on Biomedical Research (Ley 14\/ 2007 de Investigaci\u00f3n Biom\u00e9dica). All participants provided written informed consent to participate in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"JLM is currently a full-time employee of Lundbeck and has before served as a consultant or at advisory boards for the following for-profit companies or has given lectures in symposia sponsored by the following for-profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, ProMIS Neurosciences, NovoNordisk, Zamb\u00f3n, Cytox, and Nutricia. MSC has given lectures in symposia sponsored by Roche Diagnostics, S.L.U. GK and NW are full-time employees of Roche Diagnostics GmbH. IS is a full-time employee and shareholder of Roche Diagnostics International Ltd. HZ has served at scientific advisory boards and\/or as a consultant for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx, and Red Abbey Labs; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, and JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. The rest of the authors have no conflict of interest to declare. ELECSYS, COBAS, and COBAS E are trademarks of Roche. The Roche NeuroToolKit robust prototype assays are for investigational purposes only and are not approved for clinical use.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}