Neuroinflammation and tau co-localize in vivo in progressive supranuclear palsy

Objective: We examined the relationship between tau pathology and neuroinflammation using [11 C]PK11195 and [18 F]AV-1451 PET in seventeen patients with progressive supranuclear palsy Richardson's syndrome (PSP). We tested the hypothesis that neuroinflammation and tau protein aggregation co-localize macroscopically, and correlate with clinical severity. Methods: Non-displaceable binding potential (BPND ) for each ligand was quantified in 83 regions of interest (ROIs). The [11 C]PK11195 and [18 F]AV-1451 BPND values were correlated across all regions. The spatial distributions of [11 C]PK11195 and [18 F]AV-1451 binding were determined by principal component analyses (PCAs), and the loading of each spatial component compared against the patients' clinical severity (using the PSP-rating-scale). Results: Regional [11 C]PK11195 and [18 F]AV-1451 binding were positively correlated (R=0.577, p<0.0001). The PCA identified four components for each ligand, reflecting the relative expression of tau pathology or neuroinflammation in distinct groups of brain regions. Positive associations between [11 C]PK11195 and [18 F]AV-1451 components' loadings were found in both sub-cortical (R=0.769, p<0.0001) and cortical regions (R=0.836, p<0.0001). There were positive correlations between clinical severity and both sub-cortical tau pathology (R=0.667, p=0.003) and neuroinflammation (R=0.788, p<0.001). Interpretation: We show that tau pathology and neuroinflammation co-localize in PSP, and that individual differences in subcortical tau pathology and neuroinflammation are linked to clinical severity. Although longitudinal studies are needed to determine causal associations between these molecular pathologies, we suggest that the combination of tau- and immune-oriented strategies may be useful for effective disease-modifying treatments in PSP. This article is protected by copyright. All rights reserved.