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Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status

Author

Listed:
  • Alfie Wearn

    (McGill University)

  • Stéfanie A. Tremblay

    (Concordia University
    Montreal Heart Institute
    Concordia University)

  • Christine L. Tardif

    (McGill University
    McGill University
    McGill University)

  • Ilana R. Leppert

    (McGill University
    McGill University)

  • Claudine J. Gauthier

    (Concordia University
    Montreal Heart Institute
    Concordia University)

  • Giulia Baracchini

    (McGill University)

  • Colleen Hughes

    (McGill University)

  • Patrick Hewan

    (York University)

  • Jennifer Tremblay-Mercier

    (Douglas Mental Health University Institute—Research Center)

  • Pedro Rosa-Neto

    (McGill University
    McGill University
    Douglas Mental Health University Institute—Research Center)

  • Judes Poirier

    (Douglas Mental Health University Institute—Research Center
    McGill University)

  • Sylvia Villeneuve

    (McGill University
    Douglas Mental Health University Institute—Research Center
    McGill University)

  • Taylor W. Schmitz

    (Western University)

  • Gary R. Turner

    (York University)

  • R. Nathan Spreng

    (McGill University
    McGill University
    Douglas Mental Health University Institute—Research Center
    McGill University)

Abstract

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer’s disease (AD). They project broadly throughout the brain’s white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

Suggested Citation

  • Alfie Wearn & Stéfanie A. Tremblay & Christine L. Tardif & Ilana R. Leppert & Claudine J. Gauthier & Giulia Baracchini & Colleen Hughes & Patrick Hewan & Jennifer Tremblay-Mercier & Pedro Rosa-Neto & , 2024. "Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48490-z
    DOI: 10.1038/s41467-024-48490-z
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    References listed on IDEAS

    as
    1. Taylor W. Schmitz & R. Nathan Spreng, 2016. "Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    2. Joel W. Blanchard & Leyla Anne Akay & Jose Davila-Velderrain & Djuna Maydell & Hansruedi Mathys & Shawn M. Davidson & Audrey Effenberger & Chih-Yu Chen & Kristal Maner-Smith & Ihab Hajjar & Eric A. Or, 2022. "APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes," Nature, Nature, vol. 611(7937), pages 769-779, November.
    3. Annalisa Nobili & Emanuele Claudio Latagliata & Maria Teresa Viscomi & Virve Cavallucci & Debora Cutuli & Giacomo Giacovazzo & Paraskevi Krashia & Francesca Romana Rizzo & Ramona Marino & Mauro Federi, 2017. "Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
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