Comparing Tau PET Visual Interpretation with Tau PET Quantification, Cerebrospinal Fluid Biomarkers, and Longitudinal Clinical Assessment
Open accessAbstract
Background: 18 F-flortaucipir PET received FDA approval to visualize aggregated neurofibrillary tangles (NFTs) in brains of adult patients with cognitive impairment being evaluated for Alzheimer’s disease (AD). However, manufacturer’s guidelines for visual interpretation of 18 F-flortaucipir PET differ from how 18 F-flortaucipir PET has been measured in research settings using standardized uptake value ratios (SUVRs). How visual interpretation relates to 18 F-flortaucipir PET SUVR, cerebrospinal fluid (CSF) biomarkers, or longitudinal clinical assessment is not well understood. Objective: We compare various diagnostic methods in participants enrolled in longitudinal observational studies of aging and memory ( n = 189, 23 were cognitively impaired). Methods: Participants had tau PET, Aβ PET, MRI, and clinical and cognitive evaluation within 18 months ( n = 189); the majority ( n = 144) also underwent lumbar puncture. Two radiologists followed manufacturer’s guidelines for 18 F-flortaucipir PET visual interpretation. Results: Visual interpretation had high agreement with SUVR (98.4%)and moderate agreement with CSF p-tau181 (86.1%). Two participants demonstrated 18 F-flortaucipir uptake from meningiomas. Visual interpretation could not predict follow-up clinical assessment in 9.52% of cases. Conclusion: Visual interpretation was highly consistent with SUVR (discordant participants had hemorrhagic infarcts or occipital-predominant AD NFT deposition) and moderately consistent with CSF p-tau181 (discordant participants had AD pathophysiology not detectable on tau PET). However, close association between AD NFT deposition and clinical onset in group-level studies does not necessarily hold at the individual level, with discrepancies arising from atypical AD, vascular dementia, or frontotemporal dementia. A better understanding of relationships across imaging, CSF biomarkers, and clinical assessment is needed to provide appropriate diagnoses for these individuals.
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Aβ PET and tau PET are not perfectly accurate in detection of neuropathology.
“Notably, Aβ PET and tau PET are not perfectly accurate in detection of neuropathology45,46”
From Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests (2024) · cites this paper as [46]
The Results > Conclusions (page unavailable) describe limitations of 18F-flortaucipir tau PET: some NFT deposition may be missed by SUVR quantification, and non-AD conditions can produce uptake. The Aβ PET Methods section describes how scans were acquired and quantified but does not assess their accuracy against neuropathology. The paper therefore supports the tau PET part, not the claim about Aβ PET. (LLM, conf=0.83)
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References 37 · Cited by 10
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- Authors
- Chen, C. D., Ponisio, M. R., Lang, J. A., Flores, S., Schindler, S. E., Fagan, A. M., Morris, J. C., & Benzinger, T. L. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Benzinger, Tammie L.S.
- ORCID
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2023-04-17
- Volume
- 93
- Issue
- 2
- Pages
- 765-777
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC10200228
- OpenAlex
- W4366264598
- Cited by
- 10
- References
- 37
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (1745038, 2139839)
- National Institutes of Health
- Avid Radiopharmaceuticals
- Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis
- National Institute on Aging (P01AG003991, U19AG032438, T32AG058518, P30AG066444, R01AG070941, P01AG026276)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- 18F-flortaucipir, tau PET
- MeSH terms
- Alzheimer Disease, Humans, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction
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