Correlation of In Vivo [18F]Flortaucipir With Postmortem Alzheimer Disease Tau Pathology
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Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Therefore, there is a need to investigate the associations of tau PET with postmortem tau pathology in AD. Objective: To study the association of regional in vivo retention of the tau PET ligand [18F]flortaucipir (previously known as AV1451) with the density of tau neuropathology in the corresponding brain regions in a patient with AD. Design, Setting, and Participants: The patient was a man in his 40s with AD caused by a PSEN1 mutation. Between May 2015 and December 2016, he underwent 2 [18F]flortaucipir PET scans at Lund University Hospital, Lund, Sweden. Postmortem analysis was performed 12 months after the last PET scan. Tau pathology was assessed using phosphorylated tau (AT8) immunohistochemistry and Gallyas silver staining. In addition to the regional total tau pathology burden, the density of tau-positive neurites and intrasomal tau tangles were quantified using a stereology-based method. Further, β-amyloid-containing plaques were detected using 4G8 immunohistochemistry. Data were analyzed between January 2018 and August 2018. Main Outcomes and Measures: Regional standardized uptake value ratios of [18F]flortaucipir were compared with the amount of tau pathology in the corresponding brain areas. Results: In this patient, the clinical disease symptoms progressed rapidly in life, paralleled with an annual increase of tau PET retention of 20% to 40% in many cortical regions. Compared with postmortem immunohistochemistry, regional in vivo uptake of [18F]flortaucipir was correlated with the density of tau-positive neurites (AT8: rs = 0.87; P < .001; Gallyas: rs = 0.92; P < .001), intrasomal tau tangles (AT8: rs = 0.65; P = .01; Gallyas: rs = 0.84; P < .001), and total tau burden (AT8: rs = 0.84; P < .001; Gallyas: rs = 0.82; P < .001). No correlations between [18F]flortaucipir and β-amyloid pathology were found. Conclusions and Relevance: These results indicate that [18F]flortaucipir PET retention is a robust in vivo measure of the total AD tau burden.
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Neuropathological studies have shown that Tau PET correlates strongly to NFT and neuropil threads in the brain.
“Neuropathological studies have shown that Tau PET correlates strongly to NFT and neuropil threads in the brain (10)”
From Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease (2020) · cites this paper as [10]
Comparisons of in vivo Tau PET versus neuropathology data have shown good correlations between Tau PET signal and tau neuropathology quantifications, although individuals in those studies had substantial tau accumulation.
“comparisons of in vivo Tau PET versus neuropathology data have shown good correlations between Tau PET signal and tau neuropathology quantifications, although we note that individuals in those studies had substantial tau accumulation (10).”
From Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease (2020) · cites this paper as [10]
Studies comparing antemortem tau positron emission tomography imaging with autopsy have begun assessing the ability of flortaucipir to detect underlying neurofibrillary tangles in Alzheimer disease and non-Alzheimer disease dementias.
“Studies comparing antemortem tau PET imaging with autopsy have begun assessing the ability of flortaucipir to detect underlying NFTs in AD and non-AD dementias.25,26,27,28,29,30,31,32,33”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [33]
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- Authors
- Smith, R., Wibom, M., Pawlik, D., Englund, E., & Hansson, O.
- Affiliations
- Lund University (SE)
- Department of Cognitive Medicine, Ängelholm Hospital, Ängelholm, Sweden
- Corresponding author
- Smith, Ruben
- Hansson, Oskar
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2019-03-01
- Volume
- 76
- Issue
- 3
- Pages
- 310
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC6439731
- OpenAlex
- W2902217781
- Cited by
- 111
- References
- 25
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 8 · 2021: 17 · 2020: 29 · 2019: 9
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- JAMA Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- 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
- Alzheimer's disease, tau pathology, 18F-flortaucipir, tau PET imaging, neurofibrillary tangles, neuropil threads, PSEN1 mutations, standardized uptake value ratio, stereology, amyloid plaques
- MeSH terms
- Alzheimer Disease, Carbolines, Diagnosis, Humans, Male, Middle Aged, Amyloid beta-Peptides, tau Proteins, Radiopharmaceuticals, Presenilin-1
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