Dataset Information

¹⁸F-Flortaucipir in TDP-43 associated frontotemporal dementia.

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.

SUBMITTER: Smith R

PROVIDER: S-EPMC6465310 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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18F-Flortaucipir in TDP-43 associated frontotemporal dementia.

Smith R R Santillo A F AF Waldö M Landqvist ML Strandberg O O Berron D D Vestberg S S van Westen D D van Swieten J J Honer M M Hansson O O

Scientific reports 20190415 1

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 Alzheim ...[more]

PMID: 30988363

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Project description:Background: The tau positron emission tomography (PET) ligand 18F-flortaucipir binds to paired helical filaments of tau in aging and Alzheimer's disease (AD), but its utility in detecting tau aggregates in frontotemporal dementia (FTD) is uncertain.Methods: We performed 18F-flortaucipir imaging in patients with the FTD syndromes (n?=?45): nonfluent variant primary progressive aphasia (nfvPPA) (n?=?11), corticobasal syndrome (CBS) (n?=?10), behavioral variant frontotemporal dementia (bvFTD) (n?=?10), semantic variant primary progressive aphasia (svPPA) (n?=?2) and FTD associated pathogenic genetic mutations microtubule-associated protein tau (MAPT) (n?=?6), chromosome 9 open reading frame 72 (C9ORF72) (n?=?5), and progranulin (GRN) (n?=?1). All patients underwent MRI and ?-amyloid biomarker testing via 11C-PiB or cerebrospinal fluid. 18F-flortaucipir uptake in patients was compared to 53 ?-amyloid negative normal controls using voxelwise and pre-specified region of interest approaches.Results: On qualitative assessment, patients with nfvPPA showed elevated 18F-flortacupir binding in the left greater than right inferior frontal gyrus. Patients with CBS showed elevated binding in frontal white matter, with higher cortical gray matter uptake in a subset of ?-amyloid-positive patients. Five of ten patients with sporadic bvFTD demonstrated increased frontotemporal binding. MAPT mutation carriers had elevated 18F-flortaucipir retention primarily, but not exclusively, in mutations with Alzheimer's-like neurofibrillary tangles. However, tracer retention was also seen in patients with svPPA, and the mutations C9ORF72, GRN predicted to have TDP-43 pathology. Quantitative region-of-interest differences between patients and controls were seen only in inferior frontal gyrus in nfvPPA and left insula and bilateral temporal poles in MAPT carriers. No significant regional differences were found in CBS or sporadic bvFTD. Two patients underwent postmortem neuropathological examination. A patient with C9ORF72, TDP-43-type B pathology, and incidental co-pathology of scattered neurofibrillary tangles in the middle frontal, inferior temporal gyrus showed corresponding mild 18F-flortaucipir retention without additional uptake matching the widespread TDP-43 type B pathology. A patient with sporadic bvFTD demonstrated punctate inferior temporal and hippocampus tracer retention, corresponding to the area of severe argyrophilic grain disease pathology.Conclusions: 18F-flortaucipir in patients with FTD and predicted tauopathy or TDP-43 pathology demonstrated limited sensitivity and specificity. Further postmortem pathological confirmation and development of FTD tau-specific ligands are needed.

Dataset Information

¹⁸F-Flortaucipir in TDP-43 associated frontotemporal dementia.

Publications

<sup>18</sup>F-Flortaucipir in TDP-43 associated frontotemporal dementia.

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