TitleFrontotemporal dementia with the V337M mutation: Tau-PET and pathology correlations.
Publication TypeJournal Article
Year of Publication2017
AuthorsSpina S, Schonhaut DR, Boeve BF, Seeley WW, Ossenkoppele R, O'Neil JP, Lazaris A, Rosen HJ, Boxer AL, Perry DC, Miller BL, Dickson DW, Parisi JE, Jagust WJ, Murray ME, Rabinovici GD
Date Published2017 Feb 21
KeywordsAged, Brain, Carbolines, Fatal Outcome, Female, Frontotemporal Dementia, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Positron-Emission Tomography, Radiopharmaceuticals, tau Proteins

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

METHODS: mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [F]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 [F]AV1451 PET findings in a V337M mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [F]AV1451 imaging.

RESULTS: We found a strong association between topography and degree of [F]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 [F]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 [F]AV1451PET.

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

Alternate JournalNeurology
PubMed ID28130473
PubMed Central IDPMC5344079
Grant ListK23 AG045289 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
K24 AG045333 / AG / NIA NIH HHS / United States
R01 AG038791 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
R01 AG032306 / AG / NIA NIH HHS / United States
K08 AG052648 / AG / NIA NIH HHS / United States
U01 AG045390 / AG / NIA NIH HHS / United States
U54 NS092089 / NS / NINDS NIH HHS / United States