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Hippocampal GFAP-po...
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies.
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De Bastiani, Marco Antônio (author)
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Bellaver, Bruna (author)
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- Brum, Wagner S. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Souza, Debora G (author)
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Ferreira, Pamela C L (author)
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Rocha, Andreia S (author)
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Povala, Guilherme (author)
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Ferrari-Souza, João Pedro (author)
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- Lessa Benedet, Andréa (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Ashton, Nicholas J. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Karikari, Thomas (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Rosa-Neto, Pedro (author)
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Pascoal, Tharick A (author)
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Zimmer, Eduardo R (author)
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: Brain, behavior, and immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 110, s. 175-184
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https://doi.org/10.1...
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Abstract
Subject headings
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- In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released/leaked into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathologies. The molecular underpinnings behind this specificity are little explored. Here we investigated biomarker and transcriptomic associations of hippocampal GFAP-positive astrocytes with Aβ and tau pathologies in humans and mouse models.We studied 90 individuals with plasma GFAP, Aβ- and Tau-PET to investigate the association between biomarkers. Then, transcriptomic analysis in hippocampal GFAP-positive astrocytes isolated from mouse models presenting Aβ (PS2APP) or tau (P301S) pathologies was conducted to explore differentially expressed genes (DEGs), Gene Ontology terms, and protein-protein interaction networks associated with each phenotype.In humans, we found that plasma GFAP associates with Aβ but not tau pathology. Unveiling the unique nature of hippocampal GFAP-positive astrocytic responses to Aβ or tau pathologies, mouse transcriptomics showed scarce overlap of DEGs between the Aβ. and tau mouse models. While Aβ GFAP-positive astrocytes were overrepresented with DEGs associated with proteostasis and exocytosis-related processes, tau hippocampal GFAP-positive astrocytes presented greater abnormalities in functions related to DNA/RNA processing and cytoskeleton dynamics.Our results offer insights into Aβ- and tau-driven specific signatures in hippocampal GFAP-positive astrocytes. Characterizing how different underlying pathologies distinctly influence astrocyte responses is critical for the biological interpretation of astrocyte biomarkers and suggests the need to develop context-specific astrocyte targets to study AD.This study was supported by Instituto Serrapilheira, Alzheimer's Association, CAPES, CNPq and FAPERGS.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Humans
- Mice
- Animals
- Astrocytes
- metabolism
- Glial Fibrillary Acidic Protein
- metabolism
- Alzheimer Disease
- metabolism
- Amyloid beta-Peptides
- metabolism
- Biomarkers
- metabolism
- Hippocampus
- metabolism
- tau Proteins
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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De Bastiani, Mar ...
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Bellaver, Bruna
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Brum, Wagner S.
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Souza, Debora G
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Ferreira, Pamela ...
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Rocha, Andreia S
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show more...
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Povala, Guilherm ...
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Ferrari-Souza, J ...
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Lessa Benedet, A ...
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Ashton, Nicholas ...
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Karikari, Thomas
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Rosa-Neto, Pedro
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Pascoal, Tharick ...
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Zimmer, Eduardo ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Brain, behavior, ...
- By the university
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University of Gothenburg