Introduction

Mutations in the microtubule associated protein tau (MAPT) gene are a common cause of inherited frontotemporal dementia (FTD) and result in the deposition of pathological tau protein in the brain.1 Tau positron emission tomography (PET) may enhance in vivo diagnosis and testing of tau-based therapies in FTD, however, few tau ligands have been validated in FTD. The (¹⁸F)AV-1451 ligand was developed to assess in vivo tau accumulation and has consistently been shown to bind to tau in individuals with Alzheimer’s disease (AD) but less work has focused on the non-AD tauopathies, including FTD. Autoradiography studies of (¹⁸F)AV-1451 have shown strong binding in regions of neurofibrillary tangles matching the pattern of paired helical filament (PHF) immunochemistry but have not shown strong binding to non-PHF-tau.2

In (¹⁸F)AV-1451 studies conducted in FTD spectrum disorders, not only does the ligand not bind strongly to non-PHF tau, but there is significant in vivo binding reported in conditions where no tau is expected at all, for example, in patients with semantic variant primary progressive aphasia and with C9orf72 expansions where TDP-43 pathology is usually found.3 4 (¹⁸F)AV-1451 also displays both off-target binding in the basal ganglia and an age-related increase in binding in cognitively healthy controls.3 Nevertheless, this ligand has shown strong binding in a subset of FTD-causing MAPT mutations, including V337M and R406W that are associated with PHF-tau pathology.1 5 (¹⁸F)AV-1451 may therefore be useful in detecting tau pathology in some genetic forms of FTD that result in similar structural conformations of tau to that of AD. Here we describe longitudinal (¹⁸F)AV-1451 PET imaging from a patient with FTD due to a Q351R mutation located on exon 12 of the MAPT gene.6