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Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model

Author

Listed:
  • Laura K. Hamilton

    (Université de Montréal
    Université de Montréal)

  • Gaël Moquin-Beaudry

    (Université de Montréal
    Université de Montréal)

  • Chenicka L. Mangahas

    (Université de Montréal
    Université de Montréal)

  • Federico Pratesi

    (Université de Montréal
    Université de Montréal
    CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Myriam Aubin

    (CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Anne Aumont

    (Université de Montréal
    Université de Montréal
    CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Sandra E. Joppé

    (Université de Montréal
    Université de Montréal)

  • Alexandre Légiot

    (Université de Québec à Montréal (UQAM))

  • Annick Vachon

    (CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Mélanie Plourde

    (CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Catherine Mounier

    (Université de Québec à Montréal (UQAM))

  • Martine Tétreault

    (Université de Montréal
    Université de Montréal)

  • Karl J. L. Fernandes

    (Université de Montréal
    Université de Montréal
    CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

Abstract

The defining features of Alzheimer’s disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment.

Suggested Citation

  • Laura K. Hamilton & Gaël Moquin-Beaudry & Chenicka L. Mangahas & Federico Pratesi & Myriam Aubin & Anne Aumont & Sandra E. Joppé & Alexandre Légiot & Annick Vachon & Mélanie Plourde & Catherine Mounie, 2022. "Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29506-y
    DOI: 10.1038/s41467-022-29506-y
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    References listed on IDEAS

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