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Cited by 36Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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

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Salvadó, Gemma, Milà-Alomà, Marta, Shekari, Mahnaz, Ashton, Nicholas J., Operto, Grégory, Falcon, Carles, Cacciaglia, Raffaele, Minguillon, Carolina +13 more·2022·European Journal of Nuclear Medicine and Molecular Imaging
DOI 10.1007/s00259-022-05897-4PMC PMC9606048
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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 ([ 18 F]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 [ 18 F]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 [ 18 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 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.

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References 67 · Cited by 36

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Authors
Salvadó, G., Milà-Alomà, M., Shekari, M., Ashton, N. J., Operto, G., Falcon, C., Cacciaglia, R., Minguillon, C., Fauria, K., Niñerola-Baizán, A., Perissinotti, A., Benedet, A. L., Kollmorgen, G., Suridjan, I., Wild, N., Molinuevo, J. L., Zetterberg, H., Blennow, K., Suárez-Calvet, M., Gispert, J. D., & Study, O. B. O. T. A.
Affiliations
  • Instituto de Salud Carlos III (ES)
  • Universitat Pompeu Fabra (ES)
  • King's College London (GB)
  • Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
  • McGill University (CA)
  • Roche Diagnostics International AG (Switzerland) (CH)
Corresponding author
Gispert, Juan Domingo
ORCID
Venue
European Journal of Nuclear Medicine and Molecular Imaging
Publisher
Springer Science and Business Media LLC
Published
2022-07-18
Volume
49
Issue
13
Pages
4567-4579
ISSN
  • 1619-7070 (ISSN-L)
  • 1619-7089
DOI
10.1007/s00259-022-05897-4
PMC
PMC9606048
OpenAlex
W4285731045
Cited by
36
References
67
Citations by year
2026: 5 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 2
FWCI
5.05
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
Funders
  • “la Caixa” Foundation (LCF/PR/GN17/50300004)
  • Tribeca Film Institute (TriBEKa-17-519007)
  • Universities and Research Secretariat (2017-SGR-892)
  • Spanish Ministry of Science and Innovation (RYC-2013-13054, IJC2018-037478-I)
  • Instituto de Salud Carlos III (PI19/00155)
  • Eurofingers (733051102)
  • Swedish Research Council (2018-02532)
  • European Research Council (681712)
  • Swedish State Support for Clinical Research (ALFGBG-720931)
  • Alzheimer's Drug Discovery Foundation (201809-2016862)
  • AD strategic fund (ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C)
  • Olay Thon Fundation (FO2019-0228)
  • Horizon 2020 (860197)
  • UK Dementia Research Institute (2017-00915)
  • Swedish Alzheimer Foundation (AF-742881)
  • Hjärnfonden (FO2017-0243)
  • Skåne County Council's Research and Development Foundation (ALFGBG-715986)
  • European Union (JPND2019-466-236)
  • National Institutes of Health (1R01AG068398-01)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
reactive astrogliosis, Alzheimer's disease, brain glucose metabolism, glial fibrillary acidic protein, FDG uptake, amyloid-beta, tau pathology, brain hypometabolism, astrocytes, temporal lobe
MeSH terms
Alzheimer Disease, Glial Fibrillary Acidic Protein, Gliosis, Glucose, Humans, Inflammation, Biomarkers, Amyloid beta-Peptides, tau Proteins, Fluorodeoxyglucose F18

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