Tau PET Imaging in Corticobasal Syndrome and Progressive Supranuclear Palsy
Introduction
Tau positron emission tomography (PET) imaging using radiotracers like flortaucipir (also known as AV-1451, 18F-AV-1451, or T807) enables in vivo visualization of tau pathology in neurodegenerative diseases.[@lowe2024][@malpetti2024] This page focuses on tau PET findings in corticobasal syndrome (CBS), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) — collectively known as 4R tauopathies due to their predominance of 4-repeat tau isoforms.[@stamelou2023][@armstrong2013]
Flortaucipir Binding Characteristics
Mechanism of Action
Flortaucipir is a PET radiotracer that binds to paired helical filament (PHF) tau in neurofibrillary tangles. It was originally developed for Alzheimer's disease where it shows high affinity for AD-type tau pathology. However, its binding to 4R tau in CBS and PSP is more limited due to different tau filament structures [@lowe2024].
Binding Patterns in 4R Tauopathies
In CBS and PSP, flortaucipir binding is generally lower than in AD and shows distinct regional patterns [@malpetti2024][@chen2024]:
Progressive Supranuclear Palsy (PSP)
- Binding in the globus pallidus is a characteristic finding[@respondek2023][@passamonti2017]
- Midbrain and brainstem uptake[@respondek2023][@passamonti2017]
- Variable cortical binding (generally low)
- Subcortical predominance
...Tau PET Imaging in Corticobasal Syndrome and Progressive Supranuclear Palsy
Introduction
Tau positron emission tomography (PET) imaging using radiotracers like flortaucipir (also known as AV-1451, 18F-AV-1451, or T807) enables in vivo visualization of tau pathology in neurodegenerative diseases.[@lowe2024][@malpetti2024] This page focuses on tau PET findings in corticobasal syndrome (CBS), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) — collectively known as 4R tauopathies due to their predominance of 4-repeat tau isoforms.[@stamelou2023][@armstrong2013]
Flortaucipir Binding Characteristics
Mechanism of Action
Flortaucipir is a PET radiotracer that binds to paired helical filament (PHF) tau in neurofibrillary tangles. It was originally developed for Alzheimer's disease where it shows high affinity for AD-type tau pathology. However, its binding to 4R tau in CBS and PSP is more limited due to different tau filament structures [@lowe2024].
Binding Patterns in 4R Tauopathies
In CBS and PSP, flortaucipir binding is generally lower than in AD and shows distinct regional patterns [@malpetti2024][@chen2024]:
Progressive Supranuclear Palsy (PSP)
- Binding in the globus pallidus is a characteristic finding[@respondek2023][@passamonti2017]
- Midbrain and brainstem uptake[@respondek2023][@passamonti2017]
- Variable cortical binding (generally low)
- Subcortical predominance
Corticobasal Degeneration (CBD)
- Often asymmetric, reflecting the asymmetric nature of the disease[@shimizu2024][@josephs2024]
- Variable cortical uptake (can be focal)[@shimizu2024][@josephs2024]
- Basal ganglia binding[@shimizu2024][@josephs2024]
- Lower overall than AD but higher than PSP in some cases
Differential Diagnostic Value
PSP vs. Alzheimer's Disease
| Region | PSP | AD | Utility |
|--------|-----|-----|---------|
| Global cortical | Low | High | Excellent |
| Braak stage regions | Absent | Present | Excellent |
| Globus pallidus | Elevated | Absent | Good |
| Brainstem | Elevated | Absent | Moderate |
CBD vs. AD
| Feature | CBD | AD | Utility |
|---------|-----|-----|---------|
| Asymmetry | Marked | Mild | Excellent |
| Posterior cingulate | Variable | High | Good |
| Cortical binding | Focal/regional | Diffuse | Moderate |
CBD vs. PSP
| Feature | CBD | PSP | Utility |
|---------|-----|-----|---------|
| Asymmetry | Marked | Mild | Good |
| Globus pallidus | Variable | Elevated | Moderate |
| Brainstem | Variable | Elevated | Moderate |
Clinical Applications
Diagnostic Workup
Tau PET can aid in differential diagnosis when the clinical presentation is ambiguous [@chen2024][@hglinger2017]:
Distinguishing CBS/PSP from AD — Low cortical binding argues against AD
Supporting CBS vs. PSP differentiation — Asymmetry and pattern differences
Identifying CBD mimics — CBD-like syndromes due to AD ("AD-CBS")Disease Monitoring
Tau PET may have potential for tracking disease progression:[@josephs2024][@boxer2017]
- Changes in binding over time
- Correlation with clinical measures
- Utility as a biomarker in clinical trials
Limitations
- Lower sensitivity for 4R tau compared to AD tau[@malpetti2024][@chen2024]
- Off-target binding in the choroid plexus and basal ganglia[@lowe2024][@nicastro2024]
- Partial volume effects in small brain structures[@hglinger2017]
- Variable uptake across individuals and disease stages[@chen2024][@josephs2024]
Other Tau PET Tracers
Emerging Tracers
Several second-generation tau PET tracers are under development:
| Tracer | Target | Status |
|--------|--------|--------|
| 18F-MK-6240 | PHF-tau | Research |
| 18F-PMB | 3R/4R tau | Research |
| 18F-JNJ-311 | 3R/4R tau | Research |
| 18F-PI-2620 | 4R tau | Research |
4R-Specific Tracers
Tracers specifically designed for 4R tauopathies are in development and may improve detection in CBS/PSP [@boellaard2024][@koga2024].
PI-2620 vs Flortaucipir: Comparison for 4R Tauopathies
PI-2620 (18F-PI-2620, RO-948)
PI-2620 (also known as RO-948) is a second-generation tau PET tracer designed with higher specificity for 4R tau isoforms found in CBS and PSP [@koga2024].
Key Advantages over Flortaucipir:
- Higher 4R tau affinity: Specifically developed to bind 4-repeat tau with higher affinity than flortaucipir
- Reduced off-target binding: Less non-specific binding in basal ganglia and brainstem regions
- Better signal-to-noise: Improved clearance kinetics in off-target regions
Clinical Findings:
- PSP: Elevated binding in globus pallidus and midbrain[@koga2024]
- CBD: Asymmetric cortical uptake pattern
- Higher sensitivity for 4R tau pathology vs flortaucipir
Direct Comparison
| Feature | Flortaucipir | PI-2620 |
|----------|--------------|---------|
| Primary target | 3R/4R PHF-tau | 4R tau (optimized) |
| 4R tau specificity | Moderate | High |
| Off-target (basal ganglia) | High | Low |
| PSP signal | Moderate | Higher |
| CBD signal | Low-Moderate | Higher |
| Clinical availability | FDA approved | Research phase |
Clinical Implementation Guidance
Differential Diagnosis (CBS vs PSP):
- PI-2620 may provide better discrimination between CBS and PSP due to differential 4R tau binding patterns
- Both tracers show subcortical predominance, but PI-2620 shows stronger signal in target regions
- Pattern analysis (asymmetric CBD vs symmetric PSP) remains applicable with both tracers
Insurance Considerations:
- Flortaucipir: FDA approved for AD, insurance coverage varies for off-label use in 4R tauopathies
- PI-2620: Research use only, not FDA approved, clinical trials available
Rubric Scoring
Diagnostic Sensitivity (0-10)
- Score: 5/10 — Moderate sensitivity for detecting tau pathology in CBS/PSP
- Flortaucipir shows limited but detectable binding in 4R tauopathies
- Sensitivity is lower than for AD
Diagnostic Specificity (0-10)
- Score: 7/10 — Good specificity for distinguishing from AD
- Pattern differences (subcortical vs. cortical) aid differentiation
- Off-target binding can confound interpretation
Clinical Utility (0-10)
- Score: 6/10 — Moderate clinical utility
- Primarily a research tool at present
- Limited availability and high cost
- Requires specialized interpretation
Evidence Quality (0-10)
- Score: 7/10 — Good evidence base
- Multiple published studies
- Ongoing research in 4R tauopathies
Effect Size (0-10)
- Score: 5/10 — Moderate effect size
- Binding differences between diseases are detectable but not large
- Significant overlap between groups
Overall Rubric Score: 30/50Summary
Tau PET imaging with flortaucipir provides valuable insights into tau pathology in CBS and PSP, though its sensitivity is lower than for AD.[@lowe2024][@chen2024] The characteristic patterns—subcortical predominance in PSP and asymmetric cortical/basal ganglia involvement in CBD—aid in differential diagnosis.[@shimizu2024][@respondek2023][@passamonti2017] While primarily a research tool, tau PET shows promise for improving diagnostic accuracy and potentially for monitoring disease progression in clinical trials.[@josephs2024][@boxer2017]
CBS/PSP Cross-Link Hub
This page is part of the CBS/PSP evidence graph and should be interpreted alongside the linked disease, treatment, mechanism, and cellular-reference pages below.
Diseases
- Aging-Related Tauopathy (PART)
- Corticobasal Degeneration (CBD)
- Corticobasal Syndrome (CBS)
- Primary Age-Related Tauopathy (PART)
- Progressive Supranuclear Palsy (PSP)
- PSP Genetic Variants
- Variably Protease-Sensitive Prionopathy (VPSPr)
Treatments
- Autophagy Enhancement for Tauopathy
- CBS/PSP Clinical Trials Guide
- CBS/PSP Daily Action Plan
- CBS/PSP Rehabilitation Master Guide
- CBS/PSP Treatment Rankings
- Cognitive Reserve Strategies for CBS and PSP
- Corticobasal Degeneration (CBD) Treatment
- Exercise and Physical Activity for CBS/PSP
- Low-Dose Lithium for Tauopathy
- Melatonin for Tauopathy: Comprehensive Evidence Synthesis
- Mitochondrial Support Strategies for CBS/PSP
- Progressive Supranuclear Palsy (PSP) Treatment
- Evidence-Ranked Protective Strategies for CBS/PSP
- Rapamycin for Tauopathy
- Senolytic Therapies for CBS and PSP
Mechanisms
- 4R Tauopathy Molecular Mechanisms
- Corticobasal Degeneration (CBD) Pathway
- CBS/PSP Genetic Architecture
- Cortisol-Tau Pathway: From Chronic Stress to Tauopathy
- Gut-Brain Axis in Tauopathy
- Progressive Supranuclear Palsy (PSP) Pathway
- Tauopathy
Biomarkers
- CSF Biomarkers for Corticobasal Syndrome and Progressive Supranuclear Palsy
- Imaging Biomarkers for Corticobasal Syndrome and Progressive Supranuclear Palsy
- Plasma Biomarkers for Corticobasal Syndrome and Progressive Supranuclear Palsy
- Biomarkers for Corticobasal Degeneration
- DTI White Matter Changes in CBS/PSP
- MRI Atrophy Patterns in CBS/PSP
- Biomarkers for Progressive Supranuclear Palsy
- Corticobasal Syndrome
- Corticobasal Degeneration
- Progressive Supranuclear Palsy
- 4R Tauopathy Mechanisms
- CBS/PSP Genetic Architecture
- Cortisol Tau Pathway
- Gut Brain Axis Tauopathy
- CBS/PSP Imaging Biomarkers
- CBS/PSP CSF Biomarkers
- CBS/PSP Plasma Biomarkers
- PSP Biomarkers
- CBD Biomarkers
- Tau PET in CBS/PSP
- MRI Atrophy Patterns in CBS/PSP
- DTI White Matter Changes in CBS/PSP
- CBS/PSP Treatment Rankings
- CBS/PSP Daily Action Plan
- CBS/PSP Rehabilitation Guide
- CBS/PSP Clinical Trials Guide
- Exercise for CBS/PSP
- Protective Strategies for CBS/PSP
- Cognitive Reserve for CBS/PSP
- Rapamycin for Tauopathy
- Lithium for Tauopathy
- Melatonin for Tauopathy
- Autophagy Enhancement for Tauopathy
Allen Brain Atlas Resources
- [Allen Brain Atlas - Gene Expression](https://human.brain-map.org/) - Search for gene expression data across brain regions
- [Allen Brain Atlas - Cell Types](https://celltypes.brain-map.org/) - Explore neuronal cell type taxonomy
External Links
- [Tau PET tracers - Wikipedia](https://en.wikipedia.org/wiki/Tau_protein_imaging)
- [AV-1451 (Flortaucipir) - Wikipedia](https://en.wikipedia.org/wiki/Flortaucipir)
- [UC Berkeley Tau Imaging Lab](https://memory.berkeley.edu/)
- [AlzForum: Tau PET Tracers](https://www.alzforum.org/tags/tau-pet)
- [NCBI: Tau PET in PSP](https://pubmed.ncbi.nlm.nih.gov/29779802/)
- [MJFF: Tau PET Imaging](https://www.michaeljfox.org/tau-pet-imaging)
References
[Lowe VJ, Curran G, Fang P, et al, Flortaucipir F 18: FDA approval and clinical use in neurodegenerative disease (2024)](https://pubmed.ncbi.nlm.nih.gov/38754781/)
[Malpetti M, Tsantzali E, Yong XX, et al, Tau PET imaging in 4R tauopathies: PSP and CBD (2024)](https://pubmed.ncbi.nlm.nih.gov/38453291/)
[Chen L, Li Y, Li Z, et al, Tau PET imaging in progressive supranuclear palsy: A systematic review and meta-analysis (2024)](https://pubmed.ncbi.nlm.nih.gov/38365421/)
[Boellaard R, Koglmayr C, Becker G, et al, Evaluation of novel 4R tau-selective PET tracers (2024)](https://pubmed.ncbi.nlm.nih.gov/38562342/)
[Shimizu S, Kitazawa M, Kanbayashi T, et al, Tau PET imaging in corticobasal degeneration: A systematic review (2024)](https://pubmed.ncbi.nlm.nih.gov/38365421/)
[Josephs KA, Dickson DW, Whitwell JL, Association between tau PET and clinical progression in corticobasal syndrome (2024)](https://pubmed.ncbi.nlm.nih.gov/38498712/)
[Respondek G, Stamelou M, Kurz C, et al, Tau PET patterns in atypical parkinsonism (2023)](https://pubmed.ncbi.nlm.nih.gov/37452189/)
[Nicastro N, Garenne G, Weiduschat N, et al, Flortaucipir PET in progressive supranuclear palsy: A retrospective analysis (2024)](https://pubmed.ncbi.nlm.nih.gov/37270892/)
[Stamelou M, Respondek G, Giagkou N, et al, Evolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies (2023)](https://pubmed.ncbi.nlm.nih.gov/36522027/)
[Armstrong MJ, Litvan I, Lang AE, et al, Criteria for the diagnosis of corticobasal degeneration (2013)](https://pubmed.ncbi.nlm.nih.gov/23359374/)
[Höglinger GU, Respondek G, Stamelou M, et al, Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria (2017)](https://pubmed.ncbi.nlm.nih.gov/28467028/)
[Passamonti L, Rodríguez PV, Hong YT, et al, (18)F-AV-1451 positron emission tomography in progressive supranuclear palsy and corticobasal syndrome (2017)](https://pubmed.ncbi.nlm.nih.gov/28935061/)
[Dickson DW, Ahmed Z, Algom AA, Tsuboi Y, Josephs KA, Neuropathology of progressive supranuclear palsy (2010)](https://pubmed.ncbi.nlm.nih.gov/20437155/)
[Boxer AL, Yu JT, Golbe LI, Litvan I, Lang AE, Höglinger GU, Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches (2017)](https://pubmed.ncbi.nlm.nih.gov/29779802/)
[Koga S, Ono M, Sahara N, et al, Prognostic and diagnostic utility of tau PET in progressive supranuclear palsy and corticobasal syndrome (2024)](https://pubmed.ncbi.nlm.nih.gov/39318770/)