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Brain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy.
Palleis, C. (First author)DZNE* ; Quattrone, A.Extern* ; Dehsarvi, A. ; Roemer-Cassiano, S. N. ; Bernhardt, A. M.Extern* ; AL-108-231 Investigators, t. P. S. G. (Collaboration Author) ; Huppertz, H.-J. ; Malpetti, M. ; Boxer, A. L. ; Gnoerich, J.Extern* ; Frontzkowski, L. ; Levin, J.DZNE* ; Brendel, M.DZNE* ; Höglinger, G. U.DZNE* ; Franzmeier, N. ; Aiba, I. (Contributor) ; Antonini, A. (Contributor) ; Apetauerova, D. (Contributor) ; Azulay, J.-P. (Contributor) ; Martinez, E. B. (Contributor) ; Bang, J. (Contributor) ; Barone, P. (Contributor) ; Barrett, M. (Contributor) ; Bega, D. (Contributor) ; Berg, D. (Contributor) ; Corrales, K. B. (Contributor) ; Bordelon, Y. (Contributor) ; Boxer, A. L. (Contributor) ; Brandt, D. M. (Contributor)Extern* ; Brueggemann, N. (Contributor) ; Castelnovo, G. (Contributor) ; Ceravolo, R. (Contributor) ; Chuang, R. (Contributor) ; Chung, S. J. (Contributor) ; Church, A. (Contributor) ; Corvol, J.-C. (Contributor) ; Cudia, P. (Contributor) ; Dale, M. (Contributor) ; Defebvre, L. (Contributor) ; Drapier, S. (Contributor) ; Driver-Dunckley, E. D. (Contributor) ; Ebersbach, G. (Contributor) ; Eggert, K. M. (Contributor) ; Ellenbogen, A. (Contributor) ; Eusebio, A. (Contributor) ; Evans, A. H. (Contributor) ; Fedorova, N. (Contributor) ; Finger, E. (Contributor) ; Foubert-Samier, A. (Contributor) ; Ghosh, B. (Contributor) ; Golbe, L. (Contributor) ; Perez, F. G. (Contributor) ; Grossman, M. (Contributor) ; Hall, D. (Contributor) ; Hamada, K. (Contributor) ; Hasegawa, K. (Contributor) ; Hoeglinger, G. (Contributor) ; Honig, L. (Contributor) ; Houghton, D. (Contributor) ; Huang, X. (Contributor) ; Isaacson, S. (Contributor) ; Bojarski, J. K. (Contributor) ; Lang, A. E. (Contributor) ; Leigh, P. N. (Contributor) ; Research, B. (Contributor) ; Litvan, I. (Contributor) ; Lozano, J. J. L. (Contributor) ; Moreno, J. L. L. (Contributor) ; Ludolph, A. (Contributor)Extern* ; Piudo, M. R. L. (Contributor) ; Torres, I. M. (Contributor) ; McFarland, N. (Contributor) ; Meissner, W. (Contributor) ; Mestre, T. (Contributor) ; Rivera, P. M. (Contributor) ; Molho, E. (Contributor) ; Mollenhauer, B. (Contributor) ; Morris, H. R. (Contributor) ; Murata, M. (Contributor) ; Obi, T. (Contributor) ; Magne, F. O. (Contributor) ; O'Suilleabhain, P. (Contributor) ; Pahwa, R. (Contributor) ; Pantelyat, A. (Contributor) ; Pavese, N. (Contributor) ; Pokhabov, D. (Contributor) ; Prudlo, J. (Contributor)Extern* ; Rodriguez-Porcel, F. (Contributor) ; Rowe, J. (Contributor) ; Savitt, J. (Contributor) ; Schnitzler, A. (Contributor) ; Schulz, J. B. (Contributor) ; Seppi, K. (Contributor) ; Shah, B. (Contributor) ; Shill, H. (Contributor) ; Shprecher, D. (Contributor) ; Stamelou, M. (Contributor) ; Steiger, M. (Contributor) ; Takahashi, Y. (Contributor) ; Takigawa, H. (Contributor) ; Tartaglia, C. (Contributor) ; Toenges, L. (Contributor) ; Studienambulanz, K. (Contributor) ; Truong, D. (Contributor) ; Tse, W. (Contributor) ; Tuite, P. (Contributor) ; Volc, D. (Contributor) ; Wills, A. A. (Contributor) ; Woitalla, D. (Contributor) ; Xie, T. (Contributor) ; Yuasa, T. (Contributor) ; Zauber, S. E. (Contributor) ; Zesiewicz, T. (Contributor) ; Williams, D. (Contributor) ; Lafontaine, A. L. (Contributor) ; Marras, C. (Contributor) ; Jog, M. (Contributor) ; Panisset, M. (Contributor) ; Lang, A. (Contributor) ; Parker, L. (Contributor) ; Stewart, A. J. (Contributor) ; Corvol, J.-C. (Contributor) ; Azulay, J.-P. (Contributor) ; Couratier, P. (Contributor) ; Mollenhauer, B. (Contributor)Extern* ; Lorenzl, S. (Contributor) ; Ludolph, A. (Contributor)Extern* ; Benecke, R. (Contributor) ; Höglinger, G. (Contributor)Extern* ; Lipp, A. (Contributor) ; Reichmann, H. (Contributor) ; Woitalla, D. (Contributor) ; Chan, D. (Contributor) ; Zermansky, A. (Contributor) ; Burn, D. (Contributor) ; Lees, A. (Contributor) ; Boxer, A. (Contributor) ; Miller, B. L. (Contributor) ; Lobach, I. V. (Contributor) ; Roberson, E. (Contributor) ; Honig, L. (Contributor) ; Zamrini, E. (Contributor) ; Pahwa, R. (Contributor) ; Bor-Delon, Y. (Contributor) ; Driver-Dunkley, E. (Contributor) ; Lessig, S. (Contributor) ; Lew, M. (Contributor) ; Womack, K. (Contributor) ; Boeve, B. (Contributor) ; Ferrara, J. (Contributor) ; Hillis, A. (Contributor) ; Kaufer, D. (Contributor) ; Kumar, R. (Contributor) ; Xie, T. (Contributor) ; Gunzler, S. (Contributor) ; Zesiewicz, T. (Contributor) ; Dayalu, P. (Contributor) ; Golbe, L. (Contributor) ; Grossman, M. (Contributor) ; Jancovic, J. (Contributor) ; McGinnis, S. (Contributor) ; Santiago, A. (Contributor) ; Tuite, P. (Contributor) ; Isaacson, S. (Contributor) ; Leegwater-Kim, J. (Contributor) ; Litvan, I. (Contributor) ; Grossman, M. (Contributor) ; Knopman, D. S. (Contributor) ; Miller, B. L. (Contributor) ; Schneider, L. S. (Contributor) ; Doody, R. S. (Contributor) ; Golbe, L. I. (Contributor) ; Roberson, E. D. (Contributor) ; Koestler, M. (Contributor) ; Jack, C. R. (Contributor) ; Van Deerlin, V. (Contributor) ; Randolph, C. (Contributor) ; Lobach, I. V. (Contributor) ; Gozes, I. (Contributor) ; Whitaker, S. (Contributor) ; Hirman, J. (Contributor) ; Gold, M. (Contributor) ; Morimoto, B. H. (Contributor)
2025
Wiley
New York, NY
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Please use a persistent id in citations: doi:10.1002/mds.30257
Abstract: Progressive supranuclear palsy (PSP) is a neurodegenerative disease driven by 4-repeat τ pathology, which is thought to propagate across interconnected neurons.We hypothesized that interconnected brain regions exhibit correlated atrophy, and that atrophy propagates network-like from fast-declining epicenters to connected regions in PSP.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.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.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.
Keyword(s): Humans (MeSH) ; Supranuclear Palsy, Progressive: diagnostic imaging (MeSH) ; Supranuclear Palsy, Progressive: pathology (MeSH) ; Supranuclear Palsy, Progressive: physiopathology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Aged (MeSH) ; Brain: pathology (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: physiopathology (MeSH) ; Middle Aged (MeSH) ; Atrophy: pathology (MeSH) ; Gray Matter: pathology (MeSH) ; Gray Matter: diagnostic imaging (MeSH) ; Connectome (MeSH) ; Nerve Net: diagnostic imaging (MeSH) ; Nerve Net: pathology (MeSH) ; Nerve Net: physiopathology (MeSH) ; Longitudinal Studies (MeSH) ; PSP ; functional connectivity ; gray matter atrophy ; imaging ; tauopathies
Contributing Institute(s):
- Clinical Research (Munich) (Clinical Research (Munich))
- Clinical Neurodegeneration (AG Levin)
- Molecular Neurodegeneration (AG Haass)
Research Program(s):
- 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
- 352 - Disease Mechanisms (POF4-352) (POF4-352)
Appears in the scientific report
2025
Database coverage: ;
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; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz
; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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