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 ([11C]PK11195 PET), tau pathology ([18F]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.

Validation of the new pathology staging system for progressive supranuclear palsy

“…However, due to the nature of post mortem studies, time intervals between last ante mortem data collection and death varied widely between cases. To overcome this limitation we adjusted for the time interval in our analysis, taking advantage of the longitudinal data available for most patients in order to impute the scores at death [18].…”

Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes

“…Neuroinflammation has been identified by TSPO-ligand position emission tomography, in bvFTD, PPA and PSP 42,43 , where it is not only elevated but also prognostic of a more rapid decline. 44 Our results are relevant to the nosology of syndromes associated with FTLD. The diseases of bvFTD, PSP, CBS, PPA are clinically and pathologically distinct in their classical phenotypes, and there are critical differences in underlying neuropathology even where there is tauopathy.…”

“…Neuroinflammation has been identified by TSPO-ligand position emission tomography, in bvFTD, PPA and PSP 42,43 , where it is not only elevated but also prognostic of a more rapid decline. 44…”

Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes

“…For example, myo -inositol, which is concentrated in glia and elevated with neuroinflammation, had a positive loading. Neuroinflammation has been identified by TSPO-ligand position emission tomography, in bvFTD, PPA and PSP ( Bevan-Jones et al., 2020 ; Malpetti et al., 2020 ), where it is not only elevated but also prognostic of a more rapid decline ( Malpetti et al., 2020 ).…”