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, Galvan V · 2010 · PLoS ONE · Atlas ID SPI2010

What this study shows

Connected the longevity drug to a specific age-related disease. Long-term rapamycin prevented memory deficits and lowered toxic amyloid-beta in an Alzheimer's mouse model - and the benefit tracked with INCREASED autophagy in neurons. Suggested that the same autophagy boost that may slow aging could also help clear disease-causing proteins.

Abstract

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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.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: PDAPP transgenic mice (Alzheimer's model)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	PDAPP transgenic mice (Alzheimer's model)
Journal	PLoS ONE
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1371/journal.pone.0009979 · PMID 20376313 · Free full text (PMC2848616)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Rapamycin
Target	mTOR / amyloid-β
Model	PDAPP transgenic mice (Alzheimer's model)
Effect	Rapamycin reduces amyloid-β levels and abolishes cognitive deficits in an Alzheimer's mouse model
Dose	rapamycin-supplemented diet for 13 weeks starting at 4 months of age, identical to the diet that extended lifespan in mice [5]
Sample size	groups of PDAPP mice and littermate non-transgenic controls (total N=124 for cognitive tests, based on F(3,120))
Effect size	improved learning in rapamycin-fed PDAPP mice at day 4 (P=0.036); memory in rapamycin-fed PDAPP mice was indistinguishable from non-Tg groups; significantly decreased soluble Aβ42 levels in transgenic PDAPP mice (P=0.02)
Limitations	Aβ deposition was not determined

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Brain-penetrant mTOR inhibition clears aggregates in models, but human dosing has not been shown to reach the brain — and mTORC2 is needed for memory in mice.

Answers that reference this study

Discussed in the plain-language answer Is autophagy actually required for the lifespan benefit of mTOR inhibition?.

Cite this paper

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Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (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

@article{SPI2010,
  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 Galvan, V.},
  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},
  note         = {PMID: 20376313},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SPI2010) [Data set]. https://mtor-atlas.org/study/SPI2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SPI2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SPI2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SPI2010/},
  doi          = {10.5281/zenodo.22059963}
}

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