ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodegeneration
Brain atrophy and cholinergic denervation in progressive supranuclear palsy: An MRI and [18F]-FEOBV PET study
Provisionally accepted
Prabesh Kanel*
Stiven Roytman
Giulia Carli
Robert VangelJaimie BarrFotini MichalakisChristopher Chauncey SpearsPeter J. H. Scott
Roger Albin
Nicolaas Bohnen- Michigan Medicine, University of Michigan, Ann Arbor, United States
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Introduction: Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterized by a wide spectrum of motor and cognitive impairments. Structural brain imaging biomarkers, such as the Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0), are increasingly recognized as means of supporting a PSP diagnosis. These anatomic measures lack neurobiological correlates. In the present work, we investigated whether structural brain changes captured by MRPI 2.0 associate with whole-brain and regional cholinergic nerve terminal deficits in PSP. Methods: Structural magnetic resonance (MR) and vesicular acetylcholine transporter (VAChT) [¹⁸F]-fluoroethoxybenzovesamicol ([18F]-FEOBV) PET imaging was obtained in a sample of 16 PSP subjects. MRPI 2.0 index was quantified and correlated with whole brain VAChT binding using statistical parametric mapping (SPM), after adjustment for sex, dopaminergic medication dose and disease duration. Post-hoc multiple regression analyses were performed to correlate regional mean VAChT binding with MRPI 2.0 (after adjusting for the same covariates), characterizing the proportion of variance in cholinergic terminal deficits explained by this structural index. Results: Voxel-wise SPM analyses revealed that MRPI 2.0 is significantly associated with cholinergic nerve terminal loss in brainstem, especially pontomesencephalic, limbic structures, insula, basal ganglia, thalamus, and cerebellar regions. Post-hoc multiple regression analysis demonstrated that MRPI 2.0 accounts for about half of the variance in cholinergic nerve terminal integrity within relevant brain structures in PSP, showing the most robust association in the thalamus. Discussion: Structural brain changes associated with higher MRPI 2.0 index scores may be a reliable proxy measure of cholinergic terminal deficits in PSP, predominantly those in subcortical regions. Differential association of subcortical brain region cholinergic deficits with PSP-specific structural brain changes may reflect the characteristic pattern of 4R-tau pathology observed in PSP.
Keywords: Progressive supranucelar palsy, MRPI, FEOBV, PET, midbrain
Received: 30 Aug 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Kanel, Roytman, Carli, Vangel, Barr, Michalakis, Spears, Scott, Albin and Bohnen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prabesh Kanel, prabeshk@umich.edu
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