Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies
bioRxiv, ISSN: 2692-8205
2022
- 5Citations
- 1Mentions
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Metrics Details
- Citations5
- Citation Indexes5
- CrossRef5
- Mentions1
- News Mentions1
- News1
Most Recent News
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies (Updated January 16, 2023)
2023 JAN 30 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Hematology Daily -- According to news reporting based on a preprint abstract,
Article Description
Introduction: In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released 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 pathology. The molecular underpinnings behind this specificity are unexplored. Here we investigated biomarker and transcriptomic associations of GFAP-positive astrocytes with Aβ and tau pathologies in humans and mouse models. Methods: 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 applied to explore differentially expressed genes (DEGs), Gene Ontology processes, and protein-protein interaction networks associated with each phenotype. Results: In humans, we found that plasma GFAP associates with Aβ but not tau pathology. Unveiling the unique nature of GFAP-positive astrocytic responses to Aβ or tau pathology, mouse transcriptomics showed scarce overlap of DEGs between the Aβ and tau mouse models, While Aβ GFAP-positive astrocytes were overrepresented with genes 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. Conclusion: Our results offer insights into Aβ- and tau-driven specific signatures in GFAP-positive astrocytes. Characterizing how different underlying pathologies distinctly influence astrocyte responses is critical for the biological interpretation of astrocyte-related biomarker and suggests the need to develop context-specific astrocyte targets to study AD. Funding: This study was supported by Instituto Serrapilheira, Alzheimer's Association, CAPES, CNPq and FAPERGS.
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