18F-Flortaucipir in TDP-43 associated frontotemporal dementia

Retention of 18 F-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 18 F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We t...

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Bibliographic Details
Published in:Scientific reports 2019-04, Vol.9 (1), Article 6082
Main Authors: Smith, R., Santillo, A. F., Waldö, M. Landqvist, Strandberg, O., Berron, D., Vestberg, S., van Westen, D., van Swieten, J., Honer, M., Hansson, O.
Format: Article
Language:English
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Alzheimer's disease
Aphasia
Autoradiography
Dementia
Dementia disorders
Frontotemporal dementia
Humanities and Social Sciences
Magnetic resonance imaging
multidisciplinary
Mutation
Point mutation
Retention
Science
Science (multidisciplinary)
Temporal lobe
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Summary:Retention of 18 F-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 18 F-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 18 F-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 3 H-Flortaucipir was performed. SvPPA patients exhibited higher 18 F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18 F-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 18 F-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 18 F-Flortaucipir retention, indicating that 18 F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-42625-9