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Cited by 125Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement

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Lee, Seung-Hye, Le Pichon, Claire E., Adolfsson, Oskar, Gafner, Valérie, Pihlgren, Maria, Lin, Han, Solanoy, Hilda, Brendza, Robert +16 more·2016·Cell Reports
DOI 10.1016/j.celrep.2016.06.099
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Abstract

The spread of tau pathology correlates with cognitive decline in Alzheimer's disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for targeting tau. We compared efficacy in vivo and in vitro of two versions of the same tau antibody, with and without effector function, measuring tau pathology, neuron health, and microglial function. Both antibodies reduced accumulation of tau pathology in Tau-P301L transgenic mice and protected cultured neurons against extracellular tau-induced toxicity. Only the full-effector antibody enhanced tau uptake in cultured microglia, which promoted release of proinflammatory cytokines. In neuron-microglia co-cultures, only effectorless anti-tau protected neurons, suggesting full-effector tau antibodies can induce indirect toxicity via microglia. We conclude that effector function is not required for efficacy, and effectorless tau antibodies may represent a safer approach to targeting tau.

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Crossref · 10.1016/j.celrep.2016.06.099

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  • Tau antibodies block tau spreading.

    “tau antibodies have been shown to block tau spreading36,37”

    From Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs) (2018) · cites this paper as [37]

  • The effectorless tau antibody did not stimulate microglial release of IL-1β, TNF-α or IL-6 in vitro, whereas the full Fc effector containing antibody led to neuronal toxicity.

    “In addition, the effectorless tau antibody did not stimulate microglial release of IL-1β, TNF-α or IL-6 in vitro, which in the case of the full Fc effector containing antibody led to neuronal toxicity.”

    From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [184]

  • An Fc-effectorless tau antibody reduced p-tau in vivo akin to the full-effector antibody with the same epitope specificity and affinity.

    “A recent study reported that an Fc-effectorless tau antibody reduced p-tau in vivo akin to the full-effector antibody with the same epitope specificity and affinity [184].”

    From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [184]

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Authors
Lee, S.-H., Le Pichon, C. E., Adolfsson, O., Gafner, V., Pihlgren, M., Lin, H., Solanoy, H., Brendza, R., Ngu, H., Foreman, O., Chan, R., Ernst, J. A., DiCara, D., Hotzel, I., Srinivasan, K., Hansen, D. V., Atwal, J., Lu, Y., Bumbaca, D., Pfeifer, A., Watts, R. J., Muhs, A., Scearce-Levie, K., & Ayalon, G.
Affiliations
  • Genentech (US)
  • AC Immune (Switzerland) (CH)
Corresponding author
  • Muhs, Andreas
  • Scearce-Levie, Kimberly
  • Ayalon, Gai
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-08
Volume
16
Issue
6
Pages
1690-1700
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2016.06.099
OpenAlex
W2488878741
Cited by
125
References
37
Citations by year
2026: 3 · 2025: 4 · 2024: 12 · 2023: 15 · 2022: 12 · 2021: 18 · 2020: 21 · 2019: 13 · 2018: 18 · 2017: 9
FWCI
10.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
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 antibodies, Alzheimer's disease, tau pathology, antibody effector functions, microglia, inflammatory cytokines, anti-tau therapy
MeSH terms
Alzheimer Disease, Animals, Antibodies, Brain, Cells, Cultured, Mice, Transgenic, Neurons, Cytokines, tau Proteins, Microglia, Coculture Techniques

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