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Tau immunization: a cautionary tale?
Mably AJ, Kanmert D, Mc Donald JM, Liu W, Caldarone BJ, Lemere CA, O'Nuallain B, Kosik KS et al.. Neurobiology of aging, 2014-12-30
Topic: Brain proteins, microglia and lab models
The amyloid β (Aβ)-protein and microtubule-associated protein, tau, are the major components of the amyloid plaques and neurofibrillary tangles that typify Alzheimer's disease (AD) pathology. As such both Aβ and tau have long been proposed as therapeutic targets. Immunotherapy, particularly targeting Aβ, is currently the most advanced clinical strategy for treating AD. However, several Aβ-directed clinical trials have failed, and there is concern that targeting this protein may not be useful. In contrast, there is a growing optimism that tau immunotherapy may prove more efficacious. Here, for the first time, we studied the effects of chronic administration of an anti-tau monoclonal antibody (5E2) in amyloid precursor protein transgenic mice. For our animal model, we chose the J20 mouse line because prior studies had shown that the cognitive deficits in these mice require expression of tau. Despite the fact that 5E2 was present and active in the brains of immunized mice and that this antibody appeared to engage with extracellular tau, 5E2-treatment did not recover age-dependent spatial reference memory deficits. These results indicate that the memory impairment evident in J20 mice is unlikely to be mediated by a form of extracellular tau recognized by 5E2. In addition to the lack of positive effect of anti-tau immunotherapy, we also documented a significant increase in mortality among J20 mice that received 5E2. Because both the J20 mice used here and tau transgenic mice used in prior tau immunotherapy trials are imperfect models of AD our results recommend extensive preclinical testing of anti-tau antibody-based therapies using multiple mouse models and a variety of different anti-tau antibodies.
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APA 7th
Mably, A. J., Kanmert, D., Mc Donald, J. M., Liu, W., Caldarone, B. J., Lemere, C. A., et al. (2015). Tau immunization: a cautionary tale? Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2014.11.022
Vancouver
Mably AJ, Kanmert D, Mc Donald JM, Liu W, Caldarone BJ, Lemere CA, et al. Tau immunization: a cautionary tale? Neurobiology of aging. 2015. doi:10.1016/j.neurobiolaging.2014.11.022. PMID: 25619661.
BibTeX
@article{mably2015-25619661,
author = {Mably, A. J. and Kanmert, D. and Mc Donald, J. M. and Liu, W. and Caldarone, B. J. and Lemere, C. A. and O'Nuallain, B. and Kosik, K. S. and others},
title = {{Tau immunization: a cautionary tale?}},
journal = {Neurobiology of aging},
year = {2015},
doi = {10.1016/j.neurobiolaging.2014.11.022},
pmid = {25619661},
url = {https://doi.org/10.1016/j.neurobiolaging.2014.11.022}
}
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Key findings
- For our animal model, we chose the J20 mouse line because prior studies had shown that the cognitive deficits in these mice require expression of tau.
- These results indicate that the memory impairment evident in J20 mice is unlikely to be mediated by a form of extracellular tau recognized by 5E2.
- In addition to the lack of positive effect of anti-tau immunotherapy, we also documented a significant increase in mortality among J20 mice that received 5E2.
- Because both the J20 mice used here and tau transgenic mice used in prior tau immunotherapy trials are imperfect models of AD our results recommend extensive preclinical testing of anti-tau antibody-based therapies using multiple mouse models and a variety of different anti-tau antibodies.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2015 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25619661) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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