Tau follows principal axes of functional and structural brain organization in Alzheimer’s disease

Julie Ottoy, Min Su Kang, Jazlynn Xiu Min Tan, Lyndon Boone, Reinder Vos de Wael, Bo-yong Park, Gleb Bezgin, Firoza Z. Lussier, Tharick A. Pascoal, Nesrine Rahmouni, Jenna Stevenson, Jaime Fernandez Arias, Joseph Therriault, Seok-Jun Hong, Bojana Stefanovic, JoAnne McLaurin, Jean-Paul Soucy, Serge Gauthier, Boris C. Bernhardt, Sandra E. Black, Pedro Rosa-Neto and Maged Goubran ()
Additional contact information
Julie Ottoy: University of Toronto
Min Su Kang: University of Toronto
Jazlynn Xiu Min Tan: University of Toronto
Lyndon Boone: University of Toronto
Reinder Vos de Wael: McGill University
Bo-yong Park: Inha University
Gleb Bezgin: McGill University
Firoza Z. Lussier: McGill University
Tharick A. Pascoal: University of Pittsburgh
Nesrine Rahmouni: McGill University
Jenna Stevenson: McGill University
Jaime Fernandez Arias: McGill University
Joseph Therriault: McGill University
Seok-Jun Hong: Sungkyunkwan University
Bojana Stefanovic: University of Toronto
JoAnne McLaurin: University of Toronto
Jean-Paul Soucy: McGill University
Serge Gauthier: McGill University
Boris C. Bernhardt: McGill University
Sandra E. Black: University of Toronto
Pedro Rosa-Neto: McGill University
Maged Goubran: University of Toronto

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Alzheimer’s disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of network connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that the distribution of tau and reactive microglia in humans follows spatial patterns of connectivity variation, the so-called gradients of brain organization. Notably, less distinct connectivity patterns (“gradient contraction”) are associated with cognitive decline in regions with greater tau, suggesting an interaction between reduced network differentiation and tau on cognition. Furthermore, by modeling tau in subject-specific gradient space, we demonstrate that tau accumulation in the frontoparietal and temporo-occipital cortices is associated with greater baseline tau within their functionally and structurally connected hubs, respectively. Our work unveils a role for both functional and structural brain organization in pathology accumulation in AD, and supports subject-specific gradient space as a promising tool to map disease progression.

Date: 2024
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DOI: 10.1038/s41467-024-49300-2

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