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000281815 0247_ $$2doi$$a10.1002/mds.30257
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000281815 0247_ $$2ISSN$$a1531-8257
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000281815 041__ $$aEnglish
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000281815 1001_ $$0P:(DE-2719)9000852$$aPalleis, Carla$$b0$$eFirst author
000281815 245__ $$aBrain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy.
000281815 260__ $$aNew York, NY$$bWiley$$c2025
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000281815 520__ $$aProgressive 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.
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000281815 650_7 $$2Other$$aPSP
000281815 650_7 $$2Other$$afunctional connectivity
000281815 650_7 $$2Other$$agray matter atrophy
000281815 650_7 $$2Other$$aimaging
000281815 650_7 $$2Other$$atauopathies
000281815 650_2 $$2MeSH$$aHumans
000281815 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: diagnostic imaging
000281815 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: pathology
000281815 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: physiopathology
000281815 650_2 $$2MeSH$$aMale
000281815 650_2 $$2MeSH$$aFemale
000281815 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000281815 650_2 $$2MeSH$$aAged
000281815 650_2 $$2MeSH$$aBrain: pathology
000281815 650_2 $$2MeSH$$aBrain: diagnostic imaging
000281815 650_2 $$2MeSH$$aBrain: physiopathology
000281815 650_2 $$2MeSH$$aMiddle Aged
000281815 650_2 $$2MeSH$$aAtrophy: pathology
000281815 650_2 $$2MeSH$$aGray Matter: pathology
000281815 650_2 $$2MeSH$$aGray Matter: diagnostic imaging
000281815 650_2 $$2MeSH$$aConnectome
000281815 650_2 $$2MeSH$$aNerve Net: diagnostic imaging
000281815 650_2 $$2MeSH$$aNerve Net: pathology
000281815 650_2 $$2MeSH$$aNerve Net: physiopathology
000281815 650_2 $$2MeSH$$aLongitudinal Studies
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