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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 18-07-2022 | Alzheimer's Disease | Original Article

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

Authors: Gemma Salvadó, Marta Milà-Alomà, Mahnaz Shekari, Nicholas J. Ashton, Grégory Operto, Carles Falcon, Raffaele Cacciaglia, Carolina Minguillon, Karine Fauria, Aida Niñerola-Baizán, Andrés Perissinotti, Andréa L. Benedet, Gwendlyn Kollmorgen, Ivonne Suridjan, Norbert Wild, José Luis Molinuevo, Henrik Zetterberg, Kaj Blennow, Marc Suárez-Calvet, Juan Domingo Gispert, on behalf of the ALFA Study

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 13/2022

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.

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Title: Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer’s continuum
Authors: Gemma Salvadó
Marta Milà-Alomà
Mahnaz Shekari
Nicholas J. Ashton
Grégory Operto
Carles Falcon
Raffaele Cacciaglia
Carolina Minguillon
Karine Fauria
Aida Niñerola-Baizán
Andrés Perissinotti
Andréa L. Benedet
Gwendlyn Kollmorgen
Ivonne Suridjan
Norbert Wild
José Luis Molinuevo
Henrik Zetterberg
Kaj Blennow
Marc Suárez-Calvet
Juan Domingo Gispert
on behalf of the ALFA Study
Publication date: 18-07-2022
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Positron Emission Tomography
Alzheimer's Disease
Biomarkers
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 13/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05897-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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