Related Experiment Video
Updated: Mar 8, 2026
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations
Salvatore Spina1, Daniel R Schonhaut2, Bradley F Boeve2
1From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL. Salvatore.Spina@ucsf.edu.
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.
Insights
This study shows that [18F]AV1451 PET imaging can visualize tau pathology in patients with frontotemporal dementia (FTD) caused by MAPT V337M mutations. This technique helps characterize tau accumulation in specific brain regions.
Area of Science:
- Neuroimaging
- Molecular Biology
- Neuropathology
Background:
- Frontotemporal dementia (FTD) is often associated with tau protein deposition.
- Microtubule-associated protein tau (MAPT) gene mutations, such as V337M, lead to hyperphosphorylated tau accumulation.
- The PET tracer [18F]AV1451 targets tau pathology, primarily paired helical filaments found in Alzheimer disease.
Observation:
- The study investigated [18F]AV1451 PET imaging in a patient with FTD due to a MAPT V337M mutation.
- Clinical, MRI, and PET data were analyzed in the proband, his mother, and an unrelated MAPT V337M carrier.
- Postmortem studies suggest [18F]AV1451 may have limited binding to tau in non-Alzheimer tauopathies.
Findings:
- [18F]AV1451 retention strongly correlated with tau pathology distribution in related and unrelated V337M MAPT mutation carriers.
- Significant correlations were observed between regional brain atrophy on MRI and [18F]AV1451 binding.
- The proband's clinical symptoms aligned with the extent of brain atrophy and tau accumulation detected by MRI and PET.
Implications:
- [18F]AV1451 PET is a valuable tool for visualizing and characterizing tau pathology in vivo.
- This imaging approach can aid in understanding FTD associated with specific MAPT mutations.
- The findings support the potential of [18F]AV1451 for diagnosing and monitoring tauopathies linked to certain MAPT mutations.
