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      Pathologic correlations of [F-18]-AV-1451 imaging in non-Alzheimer tauopathies

      research-article
      , MD 1 , 2 , , PhD 3 , , BA 1 , 2 , , BA 1 , 2 , , BS 2 , , BS 1 , , MD, PhD 4 , , PhD 5 , , MD 6 , 7 , , MS 4 , , BS 1 , 2 , 8 , , PhD 1 , 2 , 8 , , BS 1 , , BS 2 , , PhD 1 , 2 , , MD, PhD 1 , 9 , , MD, PhD 1 , 2 , , MD 2 , , MD, MMSc 2 , , MS 10 , , MD 2 , , MD, PhD 1 , 9 , , MD, PhD 1 , 2 , , MD 2 , , MD, PhD 1 , 2
      Annals of neurology

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          Abstract

          Objective

          Recent studies have shown that PET tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer’s brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases.

          Methods

          We quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays and quantitative tau measurements in postmortem brain samples from two Progressive Supranuclear Palsy (PSP) cases and a MAPT P301L mutation carrier. They all underwent [F-18]-AV-1451 PET imaging prior to death.

          Results

          The three subjects exhibited [F-18]-AV-1451 in vivo retention predominantly in basal ganglia and midbrain. Neuropathologic examination confirmed the PSP diagnosis in the first two subjects; the MAPT P301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in grey and white matter with heaviest burden in basal ganglia. In all three cases, autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of entorhinal cortex (reflecting incidental age-related neurofibrillary tangles) and neuromelanin-containing neurons in the substantia nigra (off-target binding). The lack of a consistent significant correlation between in vivo [F-18]-AV-1541 retention and postmortem in vitro binding and tau measures in these cases suggests that this ligand has low affinity for tau lesions primarily made of straight tau filaments.

          Interpretation

          AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in these non-Alzheimer tauopathies.

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          Author and article information

          Journal
          7707449
          656
          Ann Neurol
          Ann. Neurol.
          Annals of neurology
          0364-5134
          1531-8249
          1 February 2017
          January 2017
          01 January 2018
          : 81
          : 1
          : 117-128
          Affiliations
          [1 ]MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA
          [2 ]Department of Neurology, Massachusetts General Hospital, Boston, MA
          [3 ]Department of Radiology, Massachusetts General Hospital, Boston, MA
          [4 ]Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA
          [5 ]Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA
          [6 ]Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA
          [7 ]Geriatric Research Education and Clinical Center, VA Pittsburgh Clinical System, Pittsburgh, PA
          [8 ]Harvard Neurodiscovery Center, Massachusetts General Hospital, Boston, MA
          [9 ]C.S. Kubik Neuropathology Center, Massachusetts General Hospital, Boston, MA
          [10 ]Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA
          Author notes
          Corresponding author: Teresa Gómez-Isla, MD, PhD. Neurology Department, Massachusetts General Hospital. WACC Suite 715. 15 th Parkman St. Boston MA 02114, USA. Tel. +1.617.643-5562 Fax. +1.617.726-4101. tgomezisla@ 123456mgh.harvard.edu
          Article
          PMC5319193 PMC5319193 5319193 nihpa846719
          10.1002/ana.24844
          5319193
          27997036
          f0a22229-e05a-411d-b5c0-63641dddbc11
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