TY - JOUR
T1 - Brain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy
AU - The AL-108-231 Investigators, the PASSPORT Study Group
AU - Palleis, Carla
AU - Quattrone, Andrea
AU - Dehsarvi, Amir
AU - Roemer-Cassiano, Sebastian N.
AU - Bernhardt, Alexander M.
AU - Aiba, Ikuko
AU - Antonini, Angelo
AU - Apetauerova, Diana
AU - Azulay, Jean Philippe
AU - Martinez, Ernest Balaguer
AU - Bang, Jee
AU - Barone, Paolo
AU - Barrett, Matthew
AU - Bega, Danny
AU - Berg, Daniela
AU - Corrales, Koldo Berganzo
AU - Bordelon, Yvette
AU - Boxer, Adam L.
AU - Brandt, Moritz
AU - Brueggemann, Norbert
AU - Castelnovo, Giovanni
AU - Ceravolo, Roberto
AU - Chuang, Rosalind
AU - Chung, Sun Ju
AU - Church, Alistair
AU - Corvol, Jean Christophe
AU - Cudia, Paola
AU - Dale, Marian
AU - Defebvre, Luc
AU - Drapier, Sophie
AU - Driver-Dunckley, Erika D.
AU - Ebersbach, Georg
AU - Eggert, Karla M.
AU - Ellenbogen, Aaron
AU - Eusebio, Alexandre
AU - Evans, Andrew H.
AU - Fedorova, Natalia
AU - Finger, Elizabeth
AU - Foubert-Samier, Alexandra
AU - Ghosh, Boyd
AU - Golbe, Lawrence
AU - Perez, Francisco Grandas
AU - Grossman, Murray
AU - Hall, Deborah
AU - Hamada, Kyoko
AU - Hasegawa, Kazuko
AU - Hoeglinger, Guenter
AU - Honig, Lawrence
AU - Houghton, David
AU - Tuite, Paul
N1 - Publisher Copyright:
© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2025
Y1 - 2025
N2 - 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 (ndiscovery/nvalidation = 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.
AB - 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 (ndiscovery/nvalidation = 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.
KW - PSP
KW - functional connectivity
KW - gray matter atrophy
KW - imaging
KW - tauopathies
UR - https://www.scopus.com/pages/publications/105011355963
UR - https://www.scopus.com/pages/publications/105011355963#tab=citedBy
U2 - 10.1002/mds.30257
DO - 10.1002/mds.30257
M3 - Article
C2 - 40485628
AN - SCOPUS:105011355963
SN - 0885-3185
JO - Movement Disorders
JF - Movement Disorders
ER -