PET markers of tau and neuroinflammation are co-localized in progressive supranuclear palsy

Abstract:

Background

Progressive Supranuclear Palsy (PSP) is associated with tau-protein aggregation and neuroinflammation, but it remains unclear whether these pathogenic processes are related in vivo .

Objectives

We examined the relationship between tau pathology and microglial activation using [ 18 F]AV-1451 (indexing tau burden) and [ 11 C]PK11195 (microglial activation) PET in n=17 patients with PSP-Richardson’s syndrome.

Methods

Non-displaceable binding potential (BP ND ) for each ligand was quantified in 83 regions of interest (ROIs). [ 18 F]AV-1451 and [ 11 C]PK11195 BP ND values were correlated across all ROIs. The anatomical patterns of [ 18 F]AV-1451 and [ 11 C]PK11195 binding co-localization was determined across sets of regions derived from principal component analyses (PCAs). Finally, PCA-derived brain patterns of tau pathology and neuroinflammation were linked to clinical severity.

Results

[ 18 F]AV-1451 and [ 11 C]PK11195 binding were positively related across all ROIs (r=0.577, p<0.0001). PCAs identified four components for each ligand, reflecting the relative expression of tau pathology or neuroinflammation in distinct groups of brain regions. Positive associations between [ 18 F]AV-1451 and [ 11 C]PK11195 components were found in sub-cortical (r=0.769, p<0.0001) and cortical components(r=0.836, p<0.0001). PCA-derived components reflecting tau burden (r=0.599, p=0.011) and neuroinflammation (r=0.713, p=0.001) in sub-cortical areas related to disease severity.

Conclusions

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 how these molecular pathologies are causally linked, we suggest that the combination of tau- and immune-oriented strategies may be useful for effective disease-modifying treatments in PSP.