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Targeting mTOR restores tau-induced metabolic, mitochondrial, and cognitive deficits in a tauopathy mouse model

Tang Z, Guo M, Ding Y, Wen Y, Li B, Xiao Y, Ni R, Guan Z, Qi XL · 2024 · bioRxiv (preprint) · Atlas ID TAN2024

What this study shows

In mice engineered to overexpress a phosphomimetic tau variant, one week of rapamycin reversed tau-driven mitochondrial dysfunction and rescued cognitive performance in the Morris water maze - extends the mTOR-autophagy-neurodegeneration link (already seen with Huntington's) to a direct tau-phosphorylation mechanism relevant to Alzheimer's.

Abstract

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Aim: Hyperphosphorylated tau plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Whether mammalian target of rapamycin (mTOR) directly interacts with the Tau protein at Ser214, Ser356 and Thr231 is not clear. This study aimed to investigate whether mTOR-regulated tau phosphorylation disrupts mitochondrial dynamics and function and whether rapamycin, an mTOR inhibitor, can modulate tau phosphorylation levels and attenuate AD-related alterations.

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At a glance

Evidence type PP Preprint, not peer-reviewed This is a preprint, not yet peer-reviewed -- treat its findings as provisional until formal publication. Preprints carry their own marker because peer-review status is a different question from which system was studied.
Study typePreprint
Model systemMouse (Tau3E-overexpressing, hippocampal CA3)
JournalbioRxiv (preprint)
Year2024
Peer reviewedNo
Record last updated2026-08-22
SourceDOI 10.1101/2024.11.24.625068

Extracted findings

InterventionRapamycin (mTOR inhibition)
TargetmTOR / Tau (Ser214/Ser356/Thr231)
ModelMouse (tauopathy, Tau3E CA3)
EffectTargeting mTOR restores tau-induced metabolic, mitochondrial and cognitive deficits in a tauopathy model

In the Atlas

Related topics

Huntington's diseaseRapamycinmTORC1

Open questions that cite this study

More studies on this topic

Cite this paper

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Tang, Z., Guo, M., Ding, Y., Wen, Y., Li, B., Xiao, Y., Ni, R., Guan, Z., & Qi, X. L. (2024). Targeting mTOR restores tau-induced metabolic, mitochondrial, and cognitive deficits in a tauopathy mouse model. bioRxiv (preprint). https://doi.org/10.1101/2024.11.24.625068

@article{TAN2024,
  author       = {Tang, Z. and Guo, M. and Ding, Y. and Wen, Y. and Li, B. and Xiao, Y. and Ni, R. and Guan, Z. and Qi, X. L.},
  title        = {{Targeting mTOR restores tau-induced metabolic, mitochondrial, and cognitive deficits in a tauopathy mouse model}},
  journal      = {bioRxiv (preprint)},
  year         = {2024},
  doi          = {10.1101/2024.11.24.625068},
}

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 TAN2024) [Data set]. https://mtor-atlas.org/study/TAN2024/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_TAN2024,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record TAN2024},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/TAN2024/},
  doi          = {10.5281/zenodo.22059963}
}