Tau-Targeted Immunization Impedes Progression of Neurofibrillary Histopathology in Aged P301L Tau Transgenic Mice
Open accessAbstract
In Alzheimer's disease (AD) brains, the microtubule-associated protein tau and amyloid-β (Aβ) deposit as intracellular neurofibrillary tangles (NFTs) and extracellular plaques, respectively. Tau deposits are furthermore found in a significant number of frontotemporal dementia cases. These diseases are characterized by progressive neurodegeneration, the loss of intellectual capabilities and behavioral changes. Unfortunately, the currently available therapies are limited to symptomatic relief. While active immunization against Aβ has shown efficacy in both various AD mouse models and patients with AD, immunization against pathogenic tau has only recently been shown to prevent pathology in young tau transgenic mice. However, if translated to humans, diagnosis and treatment would be routinely done when symptoms are overt, meaning that the histopathological changes have already progressed. Therefore, we used active immunization to target pathogenic tau in 4, 8, and 18 months-old P301L tau transgenic pR5 mice that have an onset of NFT pathology at 6 months of age. In all age groups, NFT pathology was significantly reduced in treated compared to control pR5 mice. Similarly, phosphorylation of tau at pathological sites was reduced. In addition, increased astrocytosis was found in the oldest treated group. Taken together, our data suggests that tau-targeted immunization slows the progression of NFT pathology in mice, with practical implications for human patients.
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Active tau immunization reduces tau pathology by targeting single or multiple phospho-epitopes, the amino terminus, full-length normal and mutant tau, or aggregated tau.
“Active tau immunization has been shown to reduce tau pathology by targeting single185, 187, 189–193 or multiple194 phospho-epitopes, the amino terminus195, full-length normal and mutant tau196, 197, or aggregated tau198.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [189]
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- Authors
- Bi, M., Ittner, A., Ke, Y. D., Götz, J., & Ittner, L. M.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Ittner, Lars M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-08
- Volume
- 6
- Issue
- 12
- Pages
- e26860
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3234245
- OpenAlex
- W2065613337
- Cited by
- 153
- References
- 29
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 9 · 2018: 15 · 2017: 19 · 2016: 10 · 2015: 16 · 2014: 29 · 2013: 25 · 2012: 6
- FWCI
- 13.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- 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
- active immunization, neurofibrillary tangles, tau phosphorylation, astrocyte activation, Alzheimer's disease, frontotemporal dementia, neurodegeneration
- MeSH terms
- Aging, Amino Acid Sequence, Animals, Gliosis, Humans, Immunity, Immunization, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Phosphorylation, Vaccination, Neurofibrillary Tangles, tau Proteins, Disease Progression, Mice
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