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Cited by 75Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Astrocytic propagation of Tau in the context of Alzheimer's disease

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Fleeman, Rebecca M., Proctor, Elizabeth A.·2021·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2021.645233PMC PMC8010320
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Abstract

More than 6 million Americans are currently living with Alzheimer's disease (AD), and the incidence is growing rapidly with our aging population. Numerous therapeutics have failed to make it to the clinic, potentially due to a focus on presumptive pathogenic proteins instead of cell-type-specific signaling mechanisms. The tau propagation hypothesis that inter-neuronal tau transfer drives AD pathology has recently garnered attention, as accumulation of pathological tau in the brain has high clinical significance in correlating with progression of cognitive AD symptoms. However, studies on tau pathology in AD are classically neuron-centric and have greatly overlooked cell-type specific effects of tau internalization, degradation, and propagation. While the contribution of microglia to tau processing and propagation is beginning to be recognized and understood, astrocytes, glial cells in the brain important for maintaining neuronal metabolic, synaptic, trophic, and immune function which can produce, internalize, degrade, and propagate tau are understudied in their ability to affect AD progression through tau pathology. Here, we showcase evidence for whether tau uptake by astrocytes may be beneficial or detrimental to neuronal health and how astrocytes and their immunometabolic functions may be key targets for future successful AD therapies.

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  • Previous studies have shown that astrocytes can internalize tau monomers, truncated pre-formed fibrils (PFFs), and tau oligomers through HSPG-independent mechanisms.

    “Previous studies have shown that astrocytes can internalize tau monomers, 13 truncated pre‐formed fibrils (PFFs), 12 and tau oligomers 11 , 41 through HSPG‐independent mechanisms. 28”

    From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [11]

    The “Tau Internalization In Astrocytes” section reports uptake of tau monomers, truncated PFFs, and aggregates, and explicitly describes monomer uptake as non-HSPG-mediated. It describes PFF uptake by phagocytosis but does not establish that PFF or oligomer uptake is HSPG-independent; it also does not specifically identify the aggregates as oligomers. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 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 [11]

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Authors
Fleeman, R. M., & Proctor, E. A.
Affiliations
Pennsylvania State University (US)
Corresponding author
Proctor, Elizabeth A.
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2021-03-17
Volume
15
Pages
645233-645233
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2021.645233
PMC
PMC8010320
OpenAlex
W3137286213
Cited by
75
References
23
Citations by year
2026: 10 · 2025: 14 · 2024: 22 · 2023: 11 · 2022: 13 · 2021: 5
FWCI
1.70
Type
journal article
Language
en
Open access
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  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Pennsylvania
  • Pennsylvania State University
  • Penn State College of Medicine
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, tau propagation, astrocytes, tau degradation, microglia, glial cells, immunometabolism, cell type-specific signaling, neurodegeneration, therapeutic target

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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