Gemma Salvadó1,2,3, Marta Milà-Alomà1,2,4, Mahnaz Shekari1,2,4, Nicholas J Ashton5,6,7,8, Grégory Operto1,2,3, Carles Falcon1,2,9, Raffaele Cacciaglia1,2,3, Carolina Minguillon1,2,3, Karine Fauria1,3, Aida Niñerola-Baizán9,10, Andrés Perissinotti9,10, Andréa L Benedet5,11, Gwendlyn Kollmorgen12, Ivonne Suridjan13, Norbert Wild12, José Luis Molinuevo1,14, Henrik Zetterberg4,15,16,17,18, Kaj Blennow4,15, Marc Suárez-Calvet19,20,21,22, Juan Domingo Gispert23,24,25. 1. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, C/ Wellington, 30, 08005, Barcelona, Spain. 2. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 3. Centro de Investigación Biomédica en Red de Fragilidad Y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. 4. Universitat Pompeu Fabra, Barcelona, Spain. 5. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 6. Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 7. Institute of Psychiatry, King's College London, Maurice Wohl Clinical Neuroscience Institute, Psychology & Neuroscience, London, UK. 8. NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK. 9. Centro de Investigación Biomédica en Red Bioingeniería, (CIBER-BBN), Biomateriales Y Nanomedicina, Barcelona, Spain. 10. Nuclear Medicine Department, Hospital Clínic Barcelona, Barcelona, Spain. 11. Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada. 12. Roche Diagnostics GmbH, Penzberg, Germany. 13. Roche Diagnostics International Ltd, Rotkreuz, Switzerland. 14. H. Lundbeck A/S, Copenhagen, Denmark. 15. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 16. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK. 17. UK Dementia Research Institute at UCL, London, UK. 18. Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China. 19. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, C/ Wellington, 30, 08005, Barcelona, Spain. msuarez@barcelonabeta.org. 20. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. msuarez@barcelonabeta.org. 21. Centro de Investigación Biomédica en Red de Fragilidad Y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. msuarez@barcelonabeta.org. 22. Servei de Neurologia, Hospital del Mar, Barcelona, Spain. msuarez@barcelonabeta.org. 23. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, C/ Wellington, 30, 08005, Barcelona, Spain. jdgispert@barcelonabeta.org. 24. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. jdgispert@barcelonabeta.org. 25. Centro de Investigación Biomédica en Red Bioingeniería, (CIBER-BBN), Biomateriales Y Nanomedicina, Barcelona, Spain. jdgispert@barcelonabeta.org.
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.
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.
Authors: Susan M Landau; Danielle Harvey; Cindee M Madison; Robert A Koeppe; Eric M Reiman; Norman L Foster; Michael W Weiner; William J Jagust Journal: Neurobiol Aging Date: 2009-08-05 Impact factor: 4.673
Authors: Sterling C Johnson; Bradley T Christian; Ozioma C Okonkwo; Jennifer M Oh; Sandra Harding; Guofan Xu; Ansel T Hillmer; Dustin W Wooten; Dhanabalan Murali; Todd E Barnhart; Lance T Hall; Annie M Racine; William E Klunk; Chester A Mathis; Barbara B Bendlin; Catherine L Gallagher; Cynthia M Carlsson; Howard A Rowley; Bruce P Hermann; N Maritza Dowling; Sanjay Asthana; Mark A Sager Journal: Neurobiol Aging Date: 2013-10-23 Impact factor: 4.673
Authors: Carolin Heller; Martha S Foiani; Katrina Moore; Rhian Convery; Martina Bocchetta; Mollie Neason; David M Cash; David Thomas; Caroline V Greaves; Ione Oc Woollacott; Rachelle Shafei; John C Van Swieten; Fermin Moreno; Raquel Sanchez-Valle; Barbara Borroni; Robert Laforce; Mario Masellis; Maria Carmela Tartaglia; Caroline Graff; Daniela Galimberti; James B Rowe; Elizabeth Finger; Matthis Synofzik; Rik Vandenberghe; Alexandre de Mendonca; Fabrizio Tagliavini; Isabel Santana; Simon Ducharme; Christopher R Butler; Alex Gerhard; Johannes Levin; Adrian Danek; Giovanni Frisoni; Sandro Sorbi; Markus Otto; Amanda J Heslegrave; Henrik Zetterberg; Jonathan D Rohrer Journal: J Neurol Neurosurg Psychiatry Date: 2020-01-14 Impact factor: 10.154
Authors: Michael T Heneka; Monica J Carson; Joseph El Khoury; Gary E Landreth; Frederic Brosseron; Douglas L Feinstein; Andreas H Jacobs; Tony Wyss-Coray; Javier Vitorica; Richard M Ransohoff; Karl Herrup; Sally A Frautschy; Bente Finsen; Guy C Brown; Alexei Verkhratsky; Koji Yamanaka; Jari Koistinaho; Eicke Latz; Annett Halle; Gabor C Petzold; Terrence Town; Dave Morgan; Mari L Shinohara; V Hugh Perry; Clive Holmes; Nicolas G Bazan; David J Brooks; Stéphane Hunot; Bertrand Joseph; Nikolaus Deigendesch; Olga Garaschuk; Erik Boddeke; Charles A Dinarello; John C Breitner; Greg M Cole; Douglas T Golenbock; Markus P Kummer Journal: Lancet Neurol Date: 2015-04 Impact factor: 44.182
Authors: Shorena Janelidze; Niklas Mattsson; Erik Stomrud; Olof Lindberg; Sebastian Palmqvist; Henrik Zetterberg; Kaj Blennow; Oskar Hansson Journal: Neurology Date: 2018-07-27 Impact factor: 9.910