Extracellular Monomeric Tau Is Internalized by Astrocytes
Open accessAbstract
Tau is a microtubule-associated protein that is expressed in neurons. However, in a group of neurodegenerative diseases named tauopathies - characterized by an increase in aggregated and/or hyperphosphorylated Tau - the protein accumulates inside other cells, such as astrocytes and microglia. Given that these glial cells do not produce Tau, its presence can be explained by internalization from the extracellular medium and consequent formation of Tau aggregates. Among internalization mechanisms, heparan sulfate proteoglycans (HSPGs) have been proposed to be responsible for fibrillary Tau uptake in various cell types. Here we studied whether monomeric Tau, which has been observed to be internalized by glial cells such as microglia, was also taken up by astrocytes. Although this Tau form was internalized from the extracellular medium by these cells, the mechanism of uptake was found to be independent of HSPGs.
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Astrocytes are active participants in tau clearance, a process critical for limiting the spread of pathological tau aggregates in AD and related tauopathies.
“astrocytes are increasingly recognized as active participants in tau clearance, a process critical for limiting the spread of pathological tau aggregates in AD and related tauopathies.”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [13]
The Results show that cultured astrocytes internalize extracellular monomeric tau. But the Discussion says this finding supports glial contribution to cell-to-cell tau propagation, not clearance that limits the spread of pathological aggregates. The paper does not demonstrate that astrocyte uptake reduces spread in AD or related tauopathies. (LLM, conf=0.87)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAstrocytes can internalize both tau monomers and higher-molecular-weight tau species.
“Previous studies have demonstrated that astrocytes can internalize both tau monomers and higher‐molecular‐weight tau species. 13 , 28”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [13]
Astrocytes can internalize tau monomers or fibrils through mechanisms independent of HSPGs.
“Astrocytes can internalize tau monomers or fibrils through mechanisms independent of HSPGs [202].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [202]
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- Authors
- Perea, J. R., López, E., Díez-Ballesteros, J. C., Ávila, J., Hernández, F., & Bolós, M.
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Corresponding author
- Bolós, Marta
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-05-01
- Volume
- 13
- Pages
- 442-442
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC6504834
- OpenAlex
- W2943016427
- Cited by
- 114
- References
- 49
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 20 · 2023: 13 · 2022: 10 · 2021: 28 · 2020: 15 · 2019: 6
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Hispana (submittedVersion, cc-by)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
- Funders
- Centro de Biología Molecular Severo Ochoa
- Ministerio de Economía y Competitividad (SAF-2014-53040-P, BFU2016-77885-P)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- tau protein, astrocytes, tauopathy, heparan sulfate proteoglycans, microglia, tau aggregation
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