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The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

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Kent, Sarah A., Spires-Jones, Tara L., Durrant, Claire S.·2020·Acta Neuropathologica
DOI 10.1007/s00401-020-02196-wPMC PMC7498448
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Abstract

Tau and amyloid beta (Aβ) are the prime suspects for driving pathology in Alzheimer’s disease (AD) and, as such, have become the focus of therapeutic development. Recent research, however, shows that these proteins have been highly conserved throughout evolution and may have crucial, physiological roles. Such functions may be lost during AD progression or be unintentionally disrupted by tau- or Aβ-targeting therapies. Tau has been revealed to be more than a simple stabiliser of microtubules, reported to play a role in a range of biological processes including myelination, glucose metabolism, axonal transport, microtubule dynamics, iron homeostasis, neurogenesis, motor function, learning and memory, neuronal excitability, and DNA protection. Aβ is similarly multifunctional, and is proposed to regulate learning and memory, angiogenesis, neurogenesis, repair leaks in the blood–brain barrier, promote recovery from injury, and act as an antimicrobial peptide and tumour suppressor. This review will discuss potential physiological roles of tau and Aβ, highlighting how changes to these functions may contribute to pathology, as well as the implications for therapeutic development. We propose that a balanced consideration of both the physiological and pathological roles of tau and Aβ will be essential for the design of safe and effective therapeutics.

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  • Tau deletion weakens Aβ clearance and enhances plaque deposition.

    “Crosstalk with tau is also evident, whereby tau deletion weakens Aβ clearance and enhances plaque deposition, underscoring the interdependence of these pathologies [38].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [38]

    The Introduction’s table lists effects of tau knockout, but not impaired Aβ clearance or increased plaque deposition. The section on physiological Aβ concentrations mentions possible clearance failure without linking it to tau deletion. Searches for tau deletion or reduction alongside Aβ clearance and plaque deposition found no passage making the claimed connection. (LLM, conf=0.76)

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Authors
Kent, S. A., Spires-Jones, T. L., & Durrant, C. S.
Affiliations
UK Dementia Research Institute (GB)
Corresponding author
Durrant, Claire S.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2020-07-29
Volume
140
Issue
4
Pages
417-447
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-020-02196-w
PMC
PMC7498448
OpenAlex
W3045897262
Cited by
446
References
43
Citations by year
2026: 52 · 2025: 85 · 2024: 96 · 2023: 74 · 2022: 73 · 2021: 56 · 2020: 10
FWCI
6.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • Wellcome (108890/Z/15/Z)
  • ARUK Race Against Dementia (RADF2019A-001)
  • European Research Council (681181)
  • Alzheimer's Research UK
  • UK Dementia Research Institute
  • Alzheimer's Society
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
tau protein, amyloid-beta, Alzheimer's disease, off-target effects, microtubule stabilization, myelination, axonal transport, iron homeostasis, neurogenesis, learning and memory, blood-brain barrier, antimicrobial peptides, tumour suppressor, conserved protein
MeSH terms
Alzheimer Disease, Animals, Humans, Amyloid beta-Peptides, tau Proteins

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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