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Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements
Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007-08-01
Topic: Brain proteins, microglia and lab models
Immunotherapies for various neurodegenerative diseases have recently emerged as a promising approach for clearing pathological protein conformers in these disorders. This type of treatment has not been assessed in models that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer's disease. Here, we present that active immunization with a phosphorylated tau epitope, in P301L tangle model mice, reduces aggregated tau in the brain and slows progression of the tangle-related behavioral phenotype. Females had more tau pathology than males but were also more receptive to the immunotherapy. The tau antibodies generated in these animals recognized pathological tau on brain sections. Performance on behavioral assays that require extensive motor coordination correlated with tau pathology in corresponding brain areas, and antibody levels against the immunogen correlated inversely with tau pathology. Interestingly, age-dependent autoantibodies that recognized recombinant tau protein but not the immunogen were detected in the P301L mice. To confirm that anti-tau antibodies could enter the brain and bind to pathological tau, FITC-tagged antibodies purified from a P301L mouse, with a high antibody titer against the immunogen, were injected into the carotid artery of P301L mice. These antibodies were subsequently detected within the brain and colocalized with PHF1 and MC1 antibodies that recognize pathological tau. Currently, no treatment is available for clearing tau aggregates. Our present findings may lead to a novel therapy targeting one of the major hallmarks of Alzheimer's disease and frontotemporal dementia.
Key findings
- Interestingly, age-dependent autoantibodies that recognized recombinant tau protein but not the immunogen were detected in the P301L mice.
- To confirm that anti-tau antibodies could enter the brain and bind to pathological tau, FITC-tagged antibodies purified from a P301L mouse, with a high antibody titer against the immunogen, were injected into the carotid artery of P301L mice.
- These antibodies were subsequently detected within the brain and colocalized with PHF1 and MC1 antibodies that recognize pathological tau.
- Currently, no treatment is available for clearing tau aggregates.
- Our present findings may lead to a novel therapy targeting one of the major hallmarks of Alzheimer's disease and frontotemporal dementia.
Why it matters
In P301L tangle model mice, active immunization against a phosphorylated tau epitope reduced aggregated tau in the brain and slowed progression of the tangle-related behavioral phenotype. This is animal research and does not yet show that tau immunotherapy works in people with Alzheimer's disease or frontotemporal dementia.
Study details
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2007 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 508 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.2 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 4 / 6 | Cited 12.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 2 / 4 | Cited 42 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Einar M. Sigurdsson: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | New York University: institution h-index 1,612 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17715348) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.2361-07.2007
- PubMed: 17715348
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Asuni, A. A., Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2007). Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.2361-07.2007
Vancouver
Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007. doi:10.1523/jneurosci.2361-07.2007. PMID: 17715348.
BibTeX
@article{asuni2007-17715348,
author = {Asuni, A. A. and Boutajangout, A. and Quartermain, D. and Sigurdsson, E. M.},
title = {{Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2007},
doi = {10.1523/jneurosci.2361-07.2007},
pmid = {17715348},
url = {https://doi.org/10.1523/jneurosci.2361-07.2007}
}
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