Palleis, C;
Quattrone, A;
Dehsarvi, A;
Roemer-Cassiano, SN;
Bernhardt, AM;
Aiba, I;
Antonini, A;
... Xie, T; + view all
(2025)
Brain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy.
Movement Disorders
, Article mds.30257. 10.1002/mds.30257.
(In press).
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Abstract
Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease driven by 4-repeat τ pathology, which is thought to propagate across interconnected neurons. Objectives: We hypothesized that interconnected brain regions exhibit correlated atrophy, and that atrophy propagates network-like from fast-declining epicenters to connected regions in PSP. Methods: We combined resting-state functional magnetic resonance imaging (fMRI) connectomics with two independent 12-month longitudinal structural magnetic resonance imaging (MRI) datasets of PSP-Richardson syndrome (PSP-RS) patients (n<inf>discovery</inf>/n<inf>validation</inf> = 114/90). MRI-based gray matter volumes were assessed for 246 regions of the Brainnetome atlas and converted to w-scores indicating local atrophy (ie, volumes adjusted for age, sex, and intracranial volume based on regression models determined in a sample of 377 healthy amyloid- and τ-negative controls from the Alzheimer's Disease Neuroimaging Initiative [ADNI]). Annual volume changes were determined for each Brainnetome region of interest using longitudinal structural MRI. Resting-state fMRI from 69 ADNI healthy controls was used to determine a connectivity template. Results: We observed pronounced atrophy and volume decline in the frontal lobe and subcortical regions bilaterally. Correlated atrophy and volume changes were found among interconnected brain regions, with regions with severe atrophy or rapid decline being strongly connected to similarly affected areas, whereas minimally affected regions were connected to less affected areas. Connectivity patterns of atrophy epicenters predicted patient level atrophy and volume decline. Conclusions: Our findings show that key subcortical and frontal brain regions undergo atrophy in PSP-RS and that gray matter atrophy expands across interconnected brain regions, supporting the view that neurodegeneration patterns may follow the trans-neuronal τ propagation pattern in PSP-RS. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| Type: | Article |
|---|---|
| Title: | Brain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mds.30257 |
| Publisher version: | https://doi.org/10.1002/mds.30257 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | PSP, functional connectivity, gray matter atrophy, imaging, tauopathies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212464 |
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