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

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, Judes Poirier, Sylvia Villeneuve, Taylor W. Schmitz, Gary R. Turner and R. Nathan Spreng ()
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Alfie Wearn: McGill University
Stéfanie A. Tremblay: Concordia University
Christine L. Tardif: McGill University
Ilana R. Leppert: McGill University
Claudine J. Gauthier: 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
Judes Poirier: Douglas Mental Health University Institute—Research Center
Sylvia Villeneuve: McGill University
Taylor W. Schmitz: Western University
Gary R. Turner: York University
R. Nathan Spreng: McGill University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48490-z

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