Frontotemporal dementia with the V337M MAPT mutation

Objective: To assess the efficacy of [¹⁸F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation.

Methods: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [¹⁸F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies. We describe clinical, structural MRI, and [¹⁸F]AV1451 PET findings in a V337M MAPT mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M MAPT carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and MAPT V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [¹⁸F]AV1451 imaging.

Results: We found a strong association between topography and degree of [¹⁸F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of [¹⁸F]AV1451 binding in the proband and a strong association between the proband's clinical presentation and the extent of regional brain atrophy and tau accumulation as assessed by structural brain MRI and [¹⁸F]AV1451PET.

Conclusion: Our study supports the usefulness of [¹⁸F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.