Characterization of tau positron emission tomography tracer [18F]AV‐1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias
Abstract
Introduction: Aggregation of tau is a hallmark of many neurodegenerative diseases, and tau imaging with positron emission tomography (PET) may allow early diagnosis and treatment monitoring. We assessed binding of the PET tracer [18 F]AV‐1451 in a range of dementias. Methods: Phosphorimaging was used to quantify binding to postmortem brain tissue from 33 patients with different, histopathologically characterized, neurodegenerative dementias. Results: [18 F]AV‐1451 showed high specific binding in cases with Alzheimer's disease (AD), moderate binding in Pick's disease and frontotemporal dementia with parkinsonism‐17, and low but displaceable binding in corticobasal degeneration, progressive supranuclear palsy, non–tau proteinopathies, and in controls without pathology. Tracer binding did not correlate with tau load within disease groups. Discussion: [18 F]AV‐1451 binds to tau in AD, and some other tauopathies. However, evidence for a non–tau binding site and lack of correlation between tracer binding and antibody staining suggest that reliable quantification of tau load with this tracer is problematic.
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The molecular target in FTD associated with TDP43 is as yet undetermined, but is unlikely to be TDP43 itself.
“The molecular target in FTD associated with TDP43 is also as yet undetermined, but is unlikely to be TDP43 itself (Marquié et al., 2015; Lowe et al., 2016; Sander et al., 2016).”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Sander et al., 2016
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 [182]
[18F]AV-1451 shows strong in vivo and post-mortem binding to tau pathology in Alzheimer's disease, but has variable affinity in healthy aging and non-AD tauopathies.
“Although [18F]AV-1451 shows strong in vivo and post-mortem binding to tau pathology in AD, it displays variable affinity in healthy aging and non-AD tauopathies28–30.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [30]
The affinity of [18F]AV-1451 for 4-repeat tau in non-AD tauopathies such as PSP is lower than its affinity for 3/4-repeat AD-related tau pathology.
“Nevertheless, we acknowledge that the affinity of [18F]AV-1451 to the 4-repeat tau in non-AD tauopathies as PSP is lower than its affinity to 3/4-repeat AD-related tau pathology29,30.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [30]
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- Authors
- Sander, K., Lashley, T., Gami, P., Gendron, T., Lythgoe, M. F., Rohrer, J. D., Schott, J. M., Revesz, T., Fox, N. C., & Årstad, E.
- Affiliations
- University College London (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Institute of Neurology Department of Molecular Neuroscience, Queen Square Brain Bank University College London London UK
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Årstad, Erik
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-02-15
- Volume
- 12
- Issue
- 11
- Pages
- 1116-1124
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2276603225
- Cited by
- 187
- References
- 9
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 12 · 2023: 6 · 2022: 13 · 2021: 13 · 2020: 25 · 2019: 27 · 2018: 24 · 2017: 32 · 2016: 17
- FWCI
- 26.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORBi (University of Liège) (submittedVersion)
- Funders
- Alzheimer’s Research UK (ARUK‐SRF2015‐2)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- 18F-AV-1451, tau PET tracers
- MeSH terms
- Aged, Brain, Carbolines, Dementia, Female, Humans, Male, Middle Aged, tau Proteins, Radiopharmaceuticals, Neurodegenerative Diseases, Protein Isoforms, Positron-Emission Tomography
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