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

Abstract

Objective: We examined the relationship between tau pathology and neuroinammation using [11C]PK11195 and [18F]AV-1451 PET in 17 patients with progressive supranuclear palsy (PSP) Richardson’s syndrome. We tested the hypothe-sis that neuroinammation and tau protein aggregation colocalize macroscopically, and correlate with clinical severity.Methods: Nondisplaceable binding potential (BPND) for each ligand was quantied in 83 regions of interest (ROIs). The[11C]PK11195 and [18F]AV-1451 BPNDvalues were correlated across all regions. The spatial distributions of [11C]PK11195 and [18F]AV-1451 binding were determined by principal component analyses (PCAs), and the loading of eachspatial component compared against the patients’ clinical severity (using the PSP rating scale).Results: Regional [11C]PK11195 and [18F]AV-1451 binding were positively correlated (R = 0.577, p < 0.0001). The PCAidentied 4 components for each ligand, reecting the relative expression of tau pathology or neuroinammation indistinct groups of brain regions. Positive associations between [11C]PK11195 and [18F]AV-1451 components’ loadingswere found in both subcortical (R = 0.769, p < 0.0001) and cortical regions (R = 0.836, p < 0.0001). There were positivecorrelations between clinical severity and both subcortical tau pathology (R = 0.667, p = 0.003) and neuroinammation(R = 0.788, p < 0.001).Interpretation: We show that tau pathology and neuroinammation colocalize in PSP, and that individual differencesin subcortical tau pathology and neuroinammation are linked to clinical severity. Although longitudinal studies areneeded to determine causal associations between these molecular pathologies, we suggest that the combination oftau- and immune-oriented strategies may be useful for effective disease-modifying treatments in PSP.