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Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease
Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, Richardson A, Strong R et al.. PloS one, 2010-04-01
Topic: Disease mechanisms in lab and animal studies
Background Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1], [2], [3], [4]. It was recently demonstrated that long-term treatment with rapamycin, an inhibitor of the mTOR pathway[5], or ablation of the mTOR target p70S6K[6] extends lifespan in mice, possibly by delaying aging. Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined. Methodology/principal findings We used rapamycin administration and behavioral tools in a mouse model of AD as well as standard biochemical and immunohistochemical measures in brain tissue to provide answers for this question. Here we show that long-term inhibition of mTOR by rapamycin prevented AD-like cognitive deficits and lowered levels of Abeta(42), a major toxic species in AD[7], in the PDAPP transgenic mouse model. These data indicate that inhibition of the mTOR pathway can reduce Abeta(42) levels in vivo and block or delay AD in mice. As expected from the inhibition of mTOR, autophagy was increased in neurons of rapamycin-treated transgenic, but not in non-transgenic, PDAPP mice, suggesting that the reduction in Abeta and the improvement in cognitive function are due in part to increased autophagy, possibly as a response to high levels of Abeta. Conclusions/significance Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease. Rapamycin, already used in clinical settings, may be a potentially effective therapeutic agent for the treatment of AD.
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APA 7th
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., et al. (2010). Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PloS one. https://doi.org/10.1371/journal.pone.0009979
Vancouver
Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PloS one. 2010. doi:10.1371/journal.pone.0009979. PMID: 20376313.
BibTeX
@article{spilman2010-20376313,
author = {Spilman, P. and Podlutskaya, N. and Hart, M. J. and Debnath, J. and Gorostiza, O. and Bredesen, D. and Richardson, A. and Strong, R. and others},
title = {{Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease}},
journal = {PloS one},
year = {2010},
doi = {10.1371/journal.pone.0009979},
pmid = {20376313},
url = {https://doi.org/10.1371/journal.pone.0009979}
}
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Key findings
- Background Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1], [2], [3], [4].
- It was recently demonstrated that long-term treatment with rapamycin, an inhibitor of the mTOR pathway[5], or ablation of the mTOR target p70S6K[6] extends lifespan in mice, possibly by delaying aging.
- These data indicate that inhibition of the mTOR pathway can reduce Abeta(42) levels in vivo and block or delay AD in mice.
- As expected from the inhibition of mTOR, autophagy was increased in neurons of rapamycin-treated transgenic, but not in non-transgenic, PDAPP mice, suggesting that the reduction in Abeta and the improvement in cognitive function are due in part to increased autophagy, possibly as a response to high levels of Abeta.
- Conclusions/significance Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease.
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / 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 multicenter collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| 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 | 2010 — 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 |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20376313) |
| Free to read | 2 / 2 | Free to read |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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