Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease

Reji Babygirija, Michelle M. Sonsalla, Jericha Mill, Isabella James, Jessica H. Han, Cara L. Green, Mariah F. Calubag, Gina Wade, Anna Tobon, John Michael, Michaela M. Trautman, Ryan Matoska, Chung Yang Yeh, Isaac Grunow, Heidi H. Pak, Michael J. Rigby, Dominique A. Baldwin, Natalie M. Niemi, John M. Denu, Luigi PuglielliJudith Simcox, Dudley W. Lamming

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.

Original languageEnglish
Article number5217
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

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