Positron emission tomography imaging of tau pathology in progressive supranuclear palsy

Abstract

Progressive supranuclear palsy is a rare form of atypical Parkinsonism that differs neuropathologically from other parkinsonian disorders. While many parkinsonian disorders such as Parkinson's disease, Lewy body dementia, and multiple system atrophy are classified as synucleinopathies, progressive supranuclear palsy is coined a tauopathy due to the aggregation of pathological tau in the brain. [F]AV-1451 (also known as [F]-T807) is a positron emission tomography radiotracer that binds to paired helical filaments of tau in Alzheimer's disease. We investigated whether [F]AV-1451 could be used as biomarker for the diagnosis and disease progression monitoring in progressive supranuclear palsy. Six progressive supranuclear palsy, six Parkinson's disease, and 10 age-matched healthy controls were recruited. An anatomical MRI and a 90-min PET scan, using [F]AV-1451, were acquired from all participants. The standardized uptake value ratio from 60 to 90 min post-injection was calculated in each region of interest, using the cerebellar cortex as a reference region. No significant differences in standardized uptake value ratios were detected in our progressive supranuclear palsy group compared to the two control groups. [F]AV-1451 may bind selectivity to the paired helical filaments in Alzheimer's disease, which differ from the straight conformation of tau filaments in progressive supranuclear palsy.

Imaging Markers of Progression in Parkinson's Disease

“…The radiotracer, [ 18 F]‐AV‐1451, a ligand that binds to paired helical filaments of tau in Alzheimer's disease (AD), has recently been used to explore its potential as a biomarker for the diagnosis and disease progression monitoring in PSP. Previous findings did not show significant tracer retention in PSP patients compared to PD and controls; however, further investigations with the same tracer showed an off‐target binding to neuromelanin‐containing neurons in the midbrain . These observations demonstrated that [ 18 F]‐AV‐1451 might be the first PET radiotracer capable of imaging neurodegeneration of the SN in parkinsonism.…”

PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins

“…A greater number of patients would allow us to confirm our results and perhaps distinguish specific patterns that might help understand how this tracer behaves in vivo. In comparison to other tau tracers (see Table ), we believe that [ 11 C]PBB3 may be more useful for atypical parkinsonism, such as PSP and CBD; however, there also seems to be nonspecific binding to other proteins, such as α‐synuclein, or nonspecific retention in cytoplasmic inclusions, which warrants further study.…”

Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers

“…Studies of in vitro binding assays using brain homogenates found that the two tau probes, PBB3 and T807, do not compete with each other for binding sites in PSP tau aggregates. Other investigations with [ 18 F]‐AV‐1451 (i.e., [ 18 F]T807) in PSP and CBS have shown preliminary findings with either increase or no retention …”