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Research paper
Flortaucipir tau PET imaging in semantic variant primary progressive aphasia
  1. Sara J Makaretz1,
  2. Megan Quimby1,
  3. Jessica Collins1,
  4. Nikos Makris2,
  5. Scott McGinnis1,3,
  6. Aaron Schultz4,5,
  7. Neil Vasdev6,
  8. Keith A Johnson3,5,6,
  9. Bradford C Dickerson1,4,5
  1. 1 Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
  2. 2 Center for Morphometric Analysis, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
  3. 3 Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  4. 4 Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
  5. 5 Alzheimer’s Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  6. 6 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Bradford C Dickerson, MGH Frontotemporal Disorders Unit, 149 13th St., Suite 2691, Charlestown, MA 02129, USA; brad.dickerson{at}mgh.harvard.edu

Abstract

Objective The semantic variant of primary progressive aphasia (svPPA) is typically associated with frontotemporal lobar degeneration (FTLD) with longTAR DNA-binding protein (TDP)-43-positive neuropil threads and dystrophic neurites (type C), and is only rarely due to a primary tauopathy or Alzheimer’s disease. We undertook this study to investigate the localisation and magnitude of the presumed tau Positron Emission Tomography (PET) tracer [18F]Flortaucipir (FTP; also known as T807 or AV1451) in patients with svPPA, hypothesising that most patients would not show tracer uptake different from controls.

Methods FTP and [11C]Pittsburgh compound B PET imaging as well as MRI were performed in seven patients with svPPA and in 20 controls. FTP signal was analysed by visual inspection and by quantitative comparison to controls, with and without partial volume correction.

Results All seven patients showed elevated FTP uptake in the anterior temporal lobe with a leftward asymmetry that was not observed in healthy controls. This elevated FTP signal, largely co-localised with atrophy, was evident on both visual inspection and quantitative cortical surface-based analysis. Five patients were amyloid negative, one was amyloid positive and one has an unknown amyloid status.

Conclusions In this series of patients with clinical profiles, structural MRI and amyloid PET imaging typical for svPPA, FTP signal was unexpectedly elevated with a spatial pattern localised to areas of atrophy. This raises questions about the possible off-target binding of this tracer to non-tau molecules associated with neurodegeneration. Further investigation with autopsy analysis will help illuminate the binding target(s) of FTP in cases of suspected FTLD-TDP neuropathology.

  • brain atrophy
  • tau PET
  • primary progressive aphasia
  • semantic dementia
  • temporallobe

This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Contributors Data collection and analysis: SJM, MQ, KAJ, BCD. Manuscript drafting: all authors.

  • Funding This study was supported by the National Institute of Deafness and Other Communication Disorders (R01 DC014296), National Institute on Aging (R21 AG051987, R01 AG046396, P01 AG036694,P50 AG00513421), and National Institute of Neurological Disorders and Stroke (R21 NS077059). This research was carried out in whole or in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically,grant number(s) S10RR021110, S10RR023043, S10RR023401.

  • Competing interests None declared.

  • Ethics approval Partners Human Research Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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