18F-Flortaucipir in TDP-43 associated frontotemporal dementia

Sci Rep. 2019 Apr 15;9(1):6082. doi: 10.1038/s41598-019-42625-9.

Abstract

Retention of 18F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if 18F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. All underwent 18F-Flortaucipir PET and MRI scanning. Data from 39 Alzheimer's Disease patients were used for comparison. PET tracer retention was assessed both at the region-of-interest (ROI) and at the voxel-level. Further, autoradiography using 3H-Flortaucipir was performed. SvPPA patients exhibited higher 18F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18F-Flortaucipir binding was slightly increased in the inferior frontal lobes in the ROI based analysis, but these results were not replicated in the voxel-based analysis. Autoradiography did not show specific binding in svPPA cases or in C9orf72-mutation carriers. In conclusion, temporal lobe 18F-Flortaucipir retention was observed in some cases of svPPA, but the uptake was of a lower magnitude compared to AD dementia. C9orf72-mutation carriers exhibited none or limited 18F-Flortaucipir retention, indicating that 18F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • C9orf72 Protein / genetics
  • Carbolines / pharmacokinetics*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Positron-Emission Tomography
  • Protein Binding
  • TDP-43 Proteinopathies / metabolism*
  • TDP-43 Proteinopathies / pathology
  • Temporal Lobe / metabolism*
  • Temporal Lobe / pathology
  • tau Proteins / metabolism*

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • Carbolines
  • DNA-Binding Proteins
  • MAPT protein, human
  • TARDBP protein, human
  • tau Proteins
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole