18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy

Abstract:

ABSTRACT

Introduction

Progressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18 F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.

Methods

Twenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18 F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18 F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18 F-AV1451 imaging measures were correlated with clinical impairment.

Results

Widespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18 F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).

Conclusion

This cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.