Sensitivity–Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration
Open accessAbstract
Objective: To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer‐related pathology and 4‐repeat tau pathology in autopsy‐confirmed frontotemporal lobar degeneration (FTLD). Methods: Twenty‐four patients had [18 F]‐flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD‐TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)‐PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta‐ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden. Results: Nine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty‐one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta‐ROI SUVRs were not elevated in Braak IV or primary age‐related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions. Interpretation: Molecular PET shows expected correlations with Alzheimer‐related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009–1022
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Amyloid PET imaging identifies individuals with amyloid deposition in the brain and can be used to differentiate underlying Alzheimer's disease from non-Alzheimer's disease disorders in people presenting with frontotemporal dementia.
“Amyloid PET imaging identifies individuals with amyloid deposition in the brain, and it can be used to differentiate underlying Alzheimer's disease from non-Alzheimer's disease disorders in people presenting with fronto temporal dementia.70”
From Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations (2022) · cites this paper as [70]
The Introduction (page unavailable) says amyloid PET tracers detect Aβ, and the Results report PET uptake corresponding to plaques at autopsy. But the Introduction says it is unclear whether a positive scan in patients presumed to have FTLD indicates a high likelihood of Alzheimer’s disease. The study included PET-positive patients with confirmed FTLD and no cases with high Alzheimer’s disease neuropathologic change, so it does not establish the claimed diagnostic differentiation. (LLM, conf=0.88)
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References 50 · Cited by 59
- Authors
- Ghirelli, A., Tosakulwong, N., Weigand, S. D., Clark, H. M., Ali, F., Botha, H., Duffy, J. R., Utianski, R. L., Buciuc, M., Murray, M. E., Labuzan, S. A., Spychalla, A. J., Pham, N. T. T., Schwarz, C. G., Senjem, M. L., Machulda, M. M., Baker, M., Rademakers, R., Filippi, M., Jack, C. R., Lowe, V. J., Parisi, J. E., Dickson, D. W., Josephs, K. A., & Whitwell, J. L.
- Affiliations
- Mayo Clinic (US)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Whitwell, Jennifer L.
- ORCID
- Ghirelli, Alma
- Tosakulwong, Nirubol
- Weigand, Stephen D.
- Clark, Heather M.
- Ali, Farwa
- Botha, Hugo
- Duffy, Joseph R.
- Utianski, Rene L.
- Buciuc, Marina
- Murray, Melissa E.
- Labuzan, Sydney A.
- Pham, Nha Trang Thu
- Schwarz, Christopher G.
- Senjem, Matthew L.
- Machulda, Mary M.
- Baker, Matthew
- Rademakers, Rosa
- Filippi, Massimo
- Jack, Clifford R.
- Lowe, Val J.
- Dickson, Dennis W.
- Josephs, Keith A.
- Whitwell, Jennifer L.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2020-09-12
- Volume
- 88
- Issue
- 5
- Pages
- 1009-1022
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC7861121
- OpenAlex
- W3082281252
- Cited by
- 59
- References
- 50
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 12 · 2023: 8 · 2022: 10 · 2021: 9 · 2020: 1
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01‐NS89757, R21‐NS94684 R01‐NS112153)
- National Institute on Deafness and Other Communication Disorders (R01‐DC010367, R01‐DC12519, R01‐DC14942)
- Avid Radiopharmaceuticals
- 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
- frontotemporal lobar degeneration, tau PET, amyloid PET, flortaucipir, Pittsburgh compound B, progressive supranuclear palsy, corticobasal degeneration, FTLD-TDP, Pick's disease, Braak staging, neurofibrillary tangles, sensitivity and specificity, entorhinal cortex, red nucleus, midbrain tegmentum
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Autoradiography, Carbolines, Female, Humans, Male, Mesencephalon, Middle Aged, Red Nucleus, Sensitivity and Specificity, Cohort Studies, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Radiopharmaceuticals, Positron-Emission Tomography, Frontotemporal Lobar Degeneration
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