Neuroinflammation predicts disease progression in progressive supranuclear palsy

Abstract:

Objective: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). We test the hypotheses that baseline in vivo assessments of regional neuroinflammation ([ 11 C]PK11195 PET), tau pathology ([ 18 F]AV-1451 PET), and atrophy (structural MRI) predict disease progression. Methods: Seventeen patients with PSP-Richardson′s syndrome underwent a baseline multi-modal imaging assessment. Disease severity was measured at baseline and serially up to 4 years with the PSP-rating-scale (average interval 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 PSP-rating-scale scores. Single-modality imaging predictors were regressed against the individuals′ estimated rate of progression to identify the prognostic value of baseline imaging markers. Results: The PCA factors reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSP-rating-scale. PCA-derived PET markers of neuroinflammation and tau pathology correlated with brain atrophy in the same regions. However, MRI markers of brain atrophy alone did not predict clinical progression. Conclusions: Molecular imaging with PET 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 for early phase clinical trials.