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Neuroinflammation predicts disease progression in progressive supranuclear palsy.

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Passamonti, Luca 
Jones, Peter Simon 
Street, Duncan 


INTRODUCTION: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). However, the prognostic value of the in vivo imaging markers for these processes in PSP remains unclear. We test the primary hypothesis that baseline in vivo imaging assessment of neuroinflammation in subcortical regions predicts clinical progression in patients with PSP. METHODS: Seventeen patients with PSP-Richardson's syndrome underwent a baseline multimodal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, [18F]AV-1451 PET for tau pathology and structural MRI. Disease severity was measured at baseline and serially up to 4 years with the Progressive Supranuclear Palsy Rating Scale (PSPRS) (average interval of 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three principal component analyses (PCAs). A linear mixed-effects model was applied to the longitudinal PSPRS scores. Single-modality imaging predictors were regressed against the individuals' estimated rate of progression to identify the prognostic value of baseline imaging markers. RESULTS: PCA components reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSPRS. PCA-derived PET markers of neuroinflammation and tau pathology correlated with regional brain volume in the same regions. However, MRI volumes alone did not predict the rate of clinical progression. CONCLUSIONS: Molecular imaging with PET for microglial activation and tau pathology can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP and the potential for PET to stratify patients in early phase clinical trials.



Aged, Brain, Disease Progression, Encephalitis, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Prognosis, Severity of Illness Index, Supranuclear Palsy, Progressive, tau Proteins

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J Neurol Neurosurg Psychiatry

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Medical Research Council (MR/P01271X/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Wellcome Trust (103838/Z/14/Z)
Medical Research Council (MR/K02308X/1)
Medical Research Council (MR/M009041/1)
National Institute for Health and Care Research (IS-BRC-1215-20014)
This study was co-funded by the National Institute for Health Research Cambridge Biomedical Research Centre (NIHR - 146281) including their financial support for the Cambridge Brain Bank; the PSP Association (“MAPT-PSP” award); the Wellcome Trust (103838); the Cambridge Trust & Sidney Sussex College Scholarship; the Medical Research Council (MR/P01271X/1); Evelyn Trust and the Cambridge Centre for Parkinson-Plus (RG95450).
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