Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments.

Caccamo A, Majumder S, Richardson A, Strong R, Oddo S · 2010 · Journal of Biological Chemistry · Atlas ID CAC2010

What this study shows

Revealed a vicious cycle: amyloid-beta RAISES mTOR activity, and high mTOR in turn blocks the autophagy needed to clear amyloid and tau - so the disease feeds itself. Rapamycin broke the loop in 3xTg-AD mice, rescuing memory and lowering BOTH amyloid and tau, with autophagy induction shown to be necessary for the reduction in amyloid levels.

Abstract

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Accumulation of amyloid-beta (Abeta) and Tau is an invariant feature of Alzheimer disease (AD). The upstream role of Abeta accumulation in the disease pathogenesis is widely accepted, and there is strong evidence showing that Abeta accumulation causes cognitive impairments. However, the molecular mechanisms linking Abeta to cognitive decline remain to be elucidated. Here we show that the buildup of Abeta increases the mammalian target of rapamycin (mTOR) signaling, whereas decreasing mTOR signaling reduces Abeta levels, thereby highlighting an interrelation between mTOR signaling and Abeta.

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: 3xTg-AD transgenic mice); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	3xTg-AD transgenic mice
Journal	Journal of Biological Chemistry
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1074/jbc.M110.100420 · PMID 20178983 · Free full text (PMC2857107)

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	Genetic/pharmacologic (amyloid-β; mTOR)
Target	mTOR / amyloid-β / Tau
Model	3xTg-AD transgenic mice
Effect	Amyloid-β accumulation increases mTOR signaling, linking Aβ to cognitive impairment

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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Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010). Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M110.100420

@article{CAC2010,
  author       = {Caccamo, A. and Majumder, S. and Richardson, A. and Strong, R. and Oddo, S.},
  title        = {{Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments}},
  journal      = {Journal of Biological Chemistry},
  year         = {2010},
  doi          = {10.1074/jbc.M110.100420},
  note         = {PMID: 20178983},
}

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 CAC2010) [Data set]. https://mtor-atlas.org/study/CAC2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_CAC2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record CAC2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/CAC2010/},
  doi          = {10.5281/zenodo.22059963}
}

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