Journal
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
Volume 49, Issue 13, Pages 4567-4579Publisher
SPRINGER
DOI: 10.1007/s00259-022-05897-4
Keywords
Glia; Gliosis; Astroglia; Reactive astrocyte; Glucose metabolism; Glucose consumption
Funding
- la Caixa Foundation [100010434, LCF/PR/GN17/50300004]
- Alzheimer's Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- TriBEKa Imaging Platform project [TriBEKa-17-519007]
- Ministry of Business and Knowledge of the Catalan Government [2017-SGR-892]
- Spanish Ministry of Science and Innovation [RYC-2013-13054]
- Instituto de Salud Carlos III [PI19/00155]
- Spanish Ministry of Science, Innovation and Universities [IJC2018-037478-I]
- EURO-FINGERS, an EU Joint Programme-Neurodegenerative Disease Research (JPND) project
- 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
- Netherlands, Netherlands Organisation for Health Research and Development (ZonMW-Memorabel) [733051102]
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-201809-2016615]
- AD Strategic Fund [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- Olav Thon Foundation
- Erling-Persson Family Foundation
- Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden [FO2019-0228]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]
- UK Dementia Research Institute at UCL
- Swedish Alzheimer Foundation [AF-742881]
- Hjarnfonden, Sweden [FO2017-0243]
- Swedish government [ALFGBG-715986]
- Swedish County Councils, the ALF-agreement [ALFGBG-715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- National Institute of Health (NIH), USA [1R01AG068398-01]
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This study aimed to investigate the association between GFAP and reactive astrogliosis with glucose consumption. The results showed that plasma GFAP was positively associated with glucose consumption in the whole brain, while CSF GFAP was only associated with glucose uptake in specific smaller areas. These associations persisted after accounting for Aβ pathology, but became negative in Aβ and tau-positive participants in similar areas of AD-related hypometabolism.
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 ([F-18]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-beta (A beta) positive. Associations between GFAP markers and [F-18]FDG uptake were studied. We also investigated whether these associations were modified by A beta and tau status (AT stages). Results Plasma GFAP was positively associated with glucose consumption in the whole brain, while CSF GFAP associations with [F-18]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 beta pathology but became negative in A beta-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.
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