18F-AV1451 pet detects tau pathology in mapt mutation carriers and correlates strongly with immunohistochemistry of tau aggregates

Research output: Contribution to journalPublished meeting abstract

Abstract

Background: The Tau PET ligand 18F-AV1451 has been shown to reliably detect paired helical filaments of tau in Alzheimer's disease, but it is not yet known whether it binds to the tau aggregates present in patients with mutations in the gene (MAPT) coding for the tau protein. Further, no study has yet compared the cerebral retention of 18F -AV1451 with the tau aggregates revealed using neuropathology. Methods: Three patients from a Swedish family carrying the R406W mutation of MAPT were assessed with cognitive tests and subjects underwent 18F-AV1451 and 18F-Flutemetamol PET scans. Further one of younger subjects also underwent an 18F-FDG PET scan. The oldest subject died two weeks after the scan and the brain was processed for neuropathology. Tau immunohistochemistry was performed on brain sections from affected and unaffected brain regions. Results: Two mutation carriers, aged 56 and 60 years, had disease durations of 5-10 years and still only exhibited mild-moderate episodic memory impairment and no clear behavioural deficits. The MRI revealed only slight cortical atrophy and 18F-AV1451 PET imaging showed uptake in the hippocampus and the temporal lobes, especially in the inferior and anterior parts (Fig 1A, B). The uptake of 18F - AV1451 correlated well with hypometabolism revealed with FGD PET in one of the subjects. The third case, 76 years, had a disease duration of ≥20 years and exhibited clear cognitive impairment, behavioural disturbances, mutism and dysphagia. The CT scan showed generalised cortical atrophy with a pronounced temporal lobe atrophy and 18F -AV1451 PET imaging revealed uptake in the temporal and frontal lobes, as well as in the basal ganglia (Fig 1 C). The regional uptake of 18F -AV1451 correlated strongly with the tau aggregates revealed using immunohistochemistry (R2 = 0.80, P <0.01; Fig 2). All cases exhibited negative amyloid (18F -flutemetamol) PET scans. Conclusions: The in vivo uptake of 18F-AV1451 reflects the regional amount of tau aggregates revealed by neuropathological examination. Further, tau pathology in MAPT mutation carriers is accurately detected with 18F -AV1451 PET, which consequently can be used to track the effects of anti-tau therapies in this patient group. (Figure Presented) .

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • endogenous compound, flortaucipir f 18, fluorodeoxyglucose f 18, adult, basal ganglion, brain cortex atrophy, brain region, case report, chemical binding, cognitive defect, computer assisted tomography, disease carrier, disease duration, dysphagia, episodic memory, frontal lobe, genetic polymorphism, hippocampus, human, human tissue, immunohistochemistry, memory disorder, middle aged, mutation, mutism, neuropathology, nuclear magnetic resonance imaging, positron emission tomography, Swedish citizen, temporal lobe
Original languageEnglish
Pages (from-to)723-724
JournalAlzheimer's and Dementia
Volume12
Issue number7 Suppl
Publication statusPublished - 2016 Jul 1
Publication categoryResearch
Peer-reviewedYes
EventAlzheimer’s Association International Conference 2016 - Metro Toronto Convention Centre, Toronto, Canada
Duration: 2016 Jul 222016 Jul 28
https://www.alz.org/aaic/about/overview.asp