Frontotemporal dementia with the V337M MAPT mutation: tau-PET and pathology correlations
- Resource Type
- Authors
- Spina, Salvatore; Schonhaut, Daniel R; Boeve, Bradley F; Seeley, William W; Ossenkoppele, Rik; O'Neil, James P; Lazaris, Andreas; Rosen, Howard J; Boxer, Adam L; Perry, David C; Miller, Bruce L; Dickson, Dennis W; Parisi, Joseph E; Jagust, William J; Murray, Melissa E; Rabinovici, Gil D
- Source
- Spina, S; Schonhaut, DR; Boeve, BF; Seeley, WW; Ossenkoppele, R; O'Neil, JP; et al.(2017). Frontotemporal dementia with the V337M MAPT mutation: tau-PET and pathology correlations. Neurology, 758-766. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/8kc2z437
Neurology, vol 88, iss 8
- Subject
- Male
Aging
Heterozygote
Clinical Sciences
tau Proteins
Neurodegenerative
Alzheimer's Disease
Rare Diseases
Fatal Outcome
mental disorders
Acquired Cognitive Impairment
2.1 Biological and endogenous factors
Humans
Aetiology
Alzheimer's Disease Related Dementias (ADRD)
Aged
Neurology & Neurosurgery
Prevention
Neurosciences
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Brain
Middle Aged
Magnetic Resonance Imaging
Brain Disorders
Frontotemporal Dementia (FTD)
Positron-Emission Tomography
Frontotemporal Dementia
Neurological
Mutation
Biomedical Imaging
Dementia
Female
Cognitive Sciences
Radiopharmaceuticals
Carbolines
- Language
ObjectiveTo 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.MethodsMAPT 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.ResultsWe 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.ConclusionOur study supports the usefulness of [18F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.