Tau Immunotherapy
Open accessAbstract
In recent years, tau immunotherapy has advanced from proof-of-concept studies [Sigurdsson EM, NIH R01AG020197, 2001; Asuni AA, et al: J Neurosci 2007;27:9115-9129], which have now been confirmed and extended by us and others. Phase I clinical trials on active and passive tau immunizations are being conducted, with several additional passive tau antibody trials likely to be initiated in the near future for Alzheimer's disease and other tauopathies. Because tau pathology correlates better with the degree of dementia than amyloid-β (Aβ) pathology, greater clinical efficacy may be achieved by clearing tau than Aβ aggregates in the later stages of the disease, when cognitive impairments become evident. Substantial insight has now been obtained regarding which epitopes to target, mechanism of action and potential toxicity, but much remains to be clarified. All of these factors likely depend on the model/disease or stage of pathology and the immunogen/antibody. Interestingly, tau antibodies interact with the protein both extra- and intracellularly, but the importance of each site for tau clearance is not well defined. Some antibodies are readily taken up into neurons, whereas others are not. It can be argued that extracellular clearance may be safer but less efficacious than intraneuronal clearance and/or sequestration to prevent secretion and further spread of tau pathology. Development of therapeutic tau antibodies has led to antibody-derived imaging probes, which are more specific than the dye-based compounds that are already in clinical trials. Such specificity may give valuable information on the pathological tau epitope profile, which could then guide the selection of therapeutic antibodies for maximal efficacy and safety. Hopefully, tau immunotherapy will be effective in clinical trials, and further advanced by mechanistic clarification in experimental models with insights from biomarkers and postmortem analyses of clinical subjects.
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Multiple groups have employed antibodies in cell and animal models to block this spreading by targeting extracellular tau.
“Multiple groups have employed antibodies in cell and animal models to block this spreading by targeting extracellular tau238.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [238]
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- Authors
- Sigurdsson, E. M.
- Affiliations
- New York University (US)
- Corresponding author
- Sigurdsson, Einar M.
- ORCID
- Sigurdsson, Einar M.
- Venue
- Neurodegenerative Diseases
- Publisher
- S. Karger AG
- Published
- 2015-11-10
- Volume
- 16
- Issue
- 1-2
- Pages
- 34-38
- ISSN
- 1660-2854 (ISSN-L)
- 1660-2862
- PMC
- PMC4777344
- OpenAlex
- W4231985646
- Cited by
- 56
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 11 · 2018: 12 · 2017: 11 · 2016: 6
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurodegenerative Diseases (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- York University
- H. Lundbeck A/S
- National Institutes of Health
- National Institute on Aging (R01AG020197, AG032611, AG 020197, R01AG032611)
- National Institute of Neurological Disorders and Stroke (NS077239, R01NS077239)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau immunotherapy, tau antibodies, Alzheimer's disease, tauopathy, active immunization, passive immunization, tau clearance, tau pathology, amyloid-beta, immunotherapy toxicity
- MeSH terms
- Alzheimer Disease, Animals, Humans, Immunotherapy, tau Proteins, Tauopathies
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