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Cited by 33Dementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatments

18F-Flortaucipir in TDP-43 associated frontotemporal dementia

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Smith, R., Santillo, A. F., Waldö, M. Landqvist, Strandberg, O., Berron, D., Vestberg, S., van Westen, D., van Swieten, J. +2 more·2019·Scientific Reports
DOI 10.1038/s41598-019-42625-9PMC PMC6465310
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Abstract

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.

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  • Initial tau PET tracers showed good specificity for cortical tau tangles but had evidence of non-specific binding in subcortical structures, suggesting they are not suitable for non-AD tauopathies.

    “The initial tau PET tracers showed good specificity for cortical tau tangles however there has been evidence of non-specific binding in subcortical structures suggesting that tau PET with these tracers is not suitable for non-AD tauopathies [179–183].”

    From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [183]

    The Introduction says flortaucipir primarily detects AD-related tau pathology, and the Discussion identifies the putamen as an off-target binding region distinct from cortical AD tau binding (page numbers unavailable). The paper does not conclude that the initial tau PET tracers as a group are unsuitable for non-AD tauopathies; it studies flortaucipir in TDP-43-associated dementia. (LLM, conf=0.84)

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Authors
Smith, R., Santillo, A. F., Waldö, M. L., Strandberg, O., Berron, D., Vestberg, S., van Westen, D., van Swieten, J., Honer, M., & Hansson, O.
Affiliations
  • Lund University (SE)
  • F. Hoffmann-La Roche AG (CH)
Corresponding author
  • Smith, R.
  • Hansson, O.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-04-15
Volume
9
Issue
1
Pages
6082-6082
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-42625-9
PMC
PMC6465310
OpenAlex
W2936754043
Cited by
33
References
5
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 2 · 2018: 1
FWCI
4.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion)
Funders
  • EC | European Research Council
  • Knut och Alice Wallenbergs Stiftelse
  • Hjärnfonden
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
18F-flortaucipir, TDP-43 proteinopathy, semantic dementia, frontotemporal dementia, amyloid PET, lateral temporal cortex, inferior frontal lobe, autoradiography, Alzheimer's disease comparison, voxel-based analysis
MeSH terms
C9orf72 Protein, Aged, Aged, 80 and over, Carbolines, DNA-Binding Proteins, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Protein Binding, Temporal Lobe, tau Proteins, Positron-Emission Tomography, TDP-43 Proteinopathies

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