Restriction of individual branched-chain amino acids has distinct effects on the development and progression of Alzheimer's disease in 3xTg mice

Babygirija R, Green CL, Sonsalla MM, Le IMF, Xiao F, Yandell S, Calubag MF, Trautman ME, Tobon A, Matoska R, Yeh CY, …, Lamming DW · 2026 · Advanced Science · Atlas ID BAB2025

What this study shows

UPDATE (was bioRxiv preprint at seed time, peer-reviewed and published in Advanced Science March 2026). Restricting individual branched-chain amino acids has distinct, sex-specific effects on cognition and AD pathology in 3xTg mice; restriction of isoleucine and valine (but not leucine) promotes metabolic health. Note: the different BCAAs act differentially on mTORC1, which is why single-amino-acid restriction matters.

Abstract

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Dietary protein regulates metabolic health and aging, with many benefits of a low protein diet resulting from reduced consumption of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. Each BCAA has distinct physiological and molecular effects, and while restriction of protein or all three BCAAs improves cognition in mouse models of Alzheimer's disease (AD), the role of each individual BCAA on AD is unknown.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (Alzheimer's disease 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	Mouse (Alzheimer's disease model)
Journal	Advanced Science
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1002/advs.202515220 · PMID 41817439 · Free full text (PMC13248761)

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	Dietary (restriction of individual BCAAs: Leu/Ile/Val)
Target	BCAAs / mTORC1
Model	Mouse (3xTg Alzheimer's model)
Effect	Individual BCAAs have distinct, sex-specific effects on Alzheimer's progression; restricting any BCAA improved short-term memory in males (isoleucine strongest), while valine restriction gave the largest cognitive benefit in females
Dose	Diets with 67% reduction of isoleucine, leucine, or valine, started at 6 months of age; duration was 9 months for body composition, 3 months for metabolic tests.
Sample size	3xTg and NTg mice of both sexes; n=5-14 per diet group per sex, varying by experiment.
Effect size	ValR diet significantly increased energy expenditure in 3xTg females (p<0.05); IleR increased energy expenditure in 3xTg males (p<0.05) and improved glucose tolerance in both sexes (p<0.05).
Limitations	not stated

In the Atlas

Cite this paper

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Babygirija, R., Green, C. L., Sonsalla, M. M., Le, I. M. F., Xiao, F., Yandell, S., Calubag, M. F., Trautman, M. E., Tobon, A., Matoska, R., Yeh, C. Y., Opara, C. I., Grunow, I., Vertein, D., Schlorf, S., Knopf, B. A., Rigby, M. J., Harris, D. A., Keller, M. P., Attie, A. D., Puglielli, L., Jang, C., & Lamming, D. W. (2026). Restriction of individual branched-chain amino acids has distinct effects on the development and progression of Alzheimer's disease in 3xTg mice. Advanced Science. https://doi.org/10.1002/advs.202515220

@article{BAB2025,
  author       = {Babygirija, R. and Green, C. L. and Sonsalla, M. M. and Le, I. M. F. and Xiao, F. and Yandell, S. and Calubag, M. F. and Trautman, M. E. and Tobon, A. and Matoska, R. and Yeh, C. Y. and Opara, C. I. and Grunow, I. and Vertein, D. and Schlorf, S. and Knopf, B. A. and Rigby, M. J. and Harris, D. A. and Keller, M. P. and Attie, A. D. and Puglielli, L. and Jang, C. and Lamming, D. W.},
  title        = {{Restriction of individual branched-chain amino acids has distinct effects on the development and progression of Alzheimer's disease in 3xTg mice}},
  journal      = {Advanced Science},
  year         = {2026},
  doi          = {10.1002/advs.202515220},
  note         = {PMID: 41817439},
}

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 BAB2025) [Data set]. https://mtor-atlas.org/study/BAB2025/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BAB2025,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BAB2025},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BAB2025/},
  doi          = {10.5281/zenodo.22059963}
}

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