Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer's continuum

Salvadó, Gemma; Milà Alomà, Marta; Shekari, Mahnaz; Operto, Grégory; Falcón, Carles; Cacciaglia, Raffaele; Minguillón, Carolina; Zetterberg, Henrik; Blennow, Kaj; Suárez-Calvet, Marc; Gispert López, Juan Domingo; ALFA Study

Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer's continuum

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dc.contributor.author Salvadó, Gemma
dc.contributor.author Milà Alomà, Marta
dc.contributor.author Shekari, Mahnaz
dc.contributor.author Operto, Grégory
dc.contributor.author Falcón, Carles
dc.contributor.author Cacciaglia, Raffaele
dc.contributor.author Minguillón, Carolina
dc.contributor.author Zetterberg, Henrik
dc.contributor.author Blennow, Kaj
dc.contributor.author Suárez-Calvet, Marc
dc.contributor.author Gispert López, Juan Domingo
dc.contributor.author ALFA Study
dc.date.accessioned 2023-02-06T07:43:39Z
dc.date.available 2023-02-06T07:43:39Z
dc.date.issued 2022
dc.description.abstract Purpose: glial activation is one of the earliest mechanisms to be altered in Alzheimer's 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 ([18F]FDG) uptake and reactive astrogliosis, by means of GFAP quantified in both plasma and CSF for the same participants. Methods: we included 314 cognitively unimpaired participants from the ALFA + cohort, 112 of whom were amyloid-β (Aβ) positive. Associations between GFAP markers and [18F]FDG uptake were studied. We also investigated whether these associations were modified by Aβ and tau status (AT stages). Results: plasma GFAP was positively associated with glucose consumption in the whole brain, while CSF GFAP associations with [18F]FDG uptake were only observed in specific smaller areas like temporal pole and superior temporal lobe. These associations persisted when accounting for biomarkers of Aβ pathology but became negative in Aβ-positive and tau-positive participants (A + T +) in similar areas of AD-related hypometabolism. Conclusions: 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.
dc.description.sponsorship The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer’s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17–519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013–13054). MSC receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva programme grant IJC2018-037478-I). CM receives funding within the context of EURO-FINGERS, an EU Joint Programme—Neurodegenerative Disease Research (JPND) project. The EURO-FINGERS project is supported through the following funding organizations under the aegis of JPND—www.jpnd.eu: Finland, Academy of Finland; Germany, Federal Ministry of Education and Research; Spain, National Institute of Health Carlos III; Luxembourg, National Research Fund; Hungary, National Research, Development and Innovation Office; and the Netherlands, Netherlands Organisation for Health Research and Development (ZonMW-Memorabel #733051102). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018–02532); the European Research Council (#681712); the Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809–2016862); the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21–831376-C, #ADSF-21–831381-C, and #ADSF-21–831377-C); the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228); the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. KB is supported by the Swedish Research Council (#2017–00915); the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809–2016615); the Swedish Alzheimer Foundation (#AF-742881); Hjärnfonden, Sweden (#FO2017-0243); the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986); the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466–236); and the National Institute of Health (NIH), USA (grant #1R01AG068398-01).
dc.format.mimetype application/pdf
dc.identifier.citation Salvadó G, Milà-Alomà M, Shekari M, Ashton NJ, Operto G, Falcon C, et al. Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer's contínuum. Eur J Nucl Med Mol Imaging. 2022 Nov; 49(13): 4567-79. DOI: 10.1007/s00259-022-05897-4
dc.identifier.doi http://dx.doi.org/10.1007/s00259-022-05897-4
dc.identifier.issn 1619-7070
dc.identifier.uri http://hdl.handle.net/10230/55624
dc.language.iso eng
dc.publisher SpringerOpen
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/RYC2013–13054
dc.rights Copyright © Salvadó G, Milà-Alomà M, Shekari M, Ashton NJ, Operto G, Falcon C, et al. 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer's continuum
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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