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

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Listed:
  • Reji Babygirija

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital
    University of Wisconsin-Madison)

  • Michelle M. Sonsalla

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital
    University of Wisconsin-Madison)

  • Jericha Mill

    (University of Wisconsin-Madison)

  • Isabella James

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Jessica H. Han

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Cara L. Green

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • Mariah F. Calubag

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital
    University of Wisconsin-Madison)

  • Gina Wade

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Anna Tobon

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • John Michael

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • Michaela M. Trautman

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital
    University of Wisconsin-Madison)

  • Ryan Matoska

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • Chung-Yang Yeh

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • Isaac Grunow

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • Heidi H. Pak

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital
    University of Wisconsin-Madison)

  • Michael J. Rigby

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Dominique A. Baldwin

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Natalie M. Niemi

    (Washington University School of Medicine in St. Louis)

  • John M. Denu

    (University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Luigi Puglielli

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital)

  • Judith Simcox

    (University of Wisconsin-Madison
    University of Wisconsin-Madison
    University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Dudley W. Lamming

    (University of Wisconsin-Madison
    William S. Middleton Memorial Veterans Hospital
    University of Wisconsin-Madison
    University of Wisconsin-Madison)

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.

Suggested Citation

  • 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 Matosk, 2024. "Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49589-z
    DOI: 10.1038/s41467-024-49589-z
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    References listed on IDEAS

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    1. Cristal M. Hill & Diana C. Albarado & Lucia G. Coco & Redin A. Spann & Md Shahjalal Khan & Emily Qualls-Creekmore & David H. Burk & Susan J. Burke & J. Jason Collier & Sangho Yu & David H. McDougal & , 2022. "FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. David E. Harrison & Randy Strong & Zelton Dave Sharp & James F. Nelson & Clinton M. Astle & Kevin Flurkey & Nancy L. Nadon & J. Erby Wilkinson & Krystyna Frenkel & Christy S. Carter & Marco Pahor & Ma, 2009. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice," Nature, Nature, vol. 460(7253), pages 392-395, July.
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