Flortaucipir tau PET imaging in semantic variant primary progressive aphasia

The semantic variant of primary progressive aphasia (svPPA) is typically associated with frontotemporal lobar degeneration (FTLD) with longTAR DNA-binding protein (TDP)-43-positive neuropil threads and dystrophic neurites (type C), and is only rarely due to a primary tauopathy or Alzheimer's disease. We undertook this study to investigate the localisation and magnitude of the presumed tau Positron Emission Tomography (PET) tracer [¹⁸F]Flortaucipir (FTP; also known as T807 or AV1451) in patients with svPPA, hypothesising that most patients would not show tracer uptake different from controls.

FTP and [¹¹C]Pittsburgh compound B PET imaging as well as MRI were performed in seven patients with svPPA and in 20 controls. FTP signal was analysed by visual inspection and by quantitative comparison to controls, with and without partial volume correction.

All seven patients showed elevated FTP uptake in the anterior temporal lobe with a leftward asymmetry that was not observed in healthy controls. This elevated FTP signal, largely co-localised with atrophy, was evident on both visual inspection and quantitative cortical surface-based analysis. Five patients were amyloid negative, one was amyloid positive and one has an unknown amyloid status.

In this series of patients with clinical profiles, structural MRI and amyloid PET imaging typical for svPPA, FTP signal was unexpectedly elevated with a spatial pattern localised to areas of atrophy. This raises questions about the possible off-target binding of this tracer to non-tau molecules associated with neurodegeneration. Further investigation with autopsy analysis will help illuminate the binding target(s) of FTP in cases of suspected FTLD-TDP neuropathology.