This page describes an integrated diagnostic approach combining multiple biomarker modalities to improve accuracy in differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and other mimics like Parkinson's disease (PD) and Alzheimer's disease (AD).
| Modality |
CBS Findings |
PSP Findings |
Accessibility |
| Tau PET (Flortaucipir) |
Asymmetric cortical uptake |
Midbrain, globus pallidus uptake |
Moderate (specialized centers) |
| Structural MRI |
Asymmetric cortical atrophy |
Midbrain atrophy, Hummingbird sign |
High |
| DTI |
Asymmetric frontoparietal WM loss |
Superior cerebellar peduncle atrophy |
Moderate |
| DaT-SPECT |
Asymmetric putaminal deficit |
Symmetric caudate/putaminal deficit |
High |
| Biomarker |
CBS Pattern |
PSP Pattern |
Utility |
| CSF NfL |
Elevated |
Elevated |
Disease progression |
| p-tau181/tau217 |
Variable |
Elevated |
Differentiate from AD |
| p-tau231 |
May be elevated |
Elevated |
PSP specificity |
| α-synuclein RT-QuIC |
Usually negative |
Usually negative |
Exclude PD |
| Tau seeding (skin biopsy) |
Positive in some |
Positive |
Emerging |
| Scale |
Domain |
CBS Sensitivity |
PSP Sensitivity |
| CBD-FRS |
Functional rating |
High |
Moderate |
| PSPRS |
PSP rating |
Low |
High |
| MDS-UPDRS |
Motor examination |
Variable |
Moderate |
| Gene |
CBS Association |
PSP Association |
| MAPT |
Rare |
Common (H1 haplotype) |
| GRN |
Associated |
Rare |
| C9orf72 |
Rare |
Rare |
| GBA |
Associated |
Associated |
flowchart TD
A["Patient with parkinsonism"] --> B{"Asymmetric onset?"}
B -->|"Yes"| C["CBS suspected"]
B -->|"No"| D{"Vertical gaze palsy?"}
D -->|"Yes"| E["PSP suspected"]
D -->|"No"| F["Consider PD or other"]
C --> G["{Rigid-akinesia<br/>dominant?}"]
E --> H["{Rigid-akinesia<br/>dominant?}"]
G -->|"Yes"| I["CBD-FRS<br/>elevated"]
G -->|"No"| J["Cortical signs<br/>present?"]
H -->|"Yes"| K["PSPRS<br/>elevated"]
H -->|"No"| L["Falls early?"]
J -->|"Yes"| M["High CBS<br/>probability"]
J -->|"No"| N["Re-evaluate"]
L -->|"Yes"| O["Moderate PSP<br/>probability"]
flowchart TD
A["Perform MRI + Tau PET"] --> B{"MRI findings"}
B --> C["Asymmetric cortical atrophy"]
B --> D["Midbrain atrophy"]
B --> E["Both"]
C --> F{"Tau PET"}
D --> G{"Tau PET"}
E --> H{"Tau PET"}
F -->|"Midbrain uptake"| I["Mixed CBS/PSP"]
F -->|"Cortical uptake"| J["CBS + AD"]
F -->|"Negative"| K["Idiopathic CBS"]
G -->|"Cortical uptake"| L["PSP + AD"]
G -->|"Negative"| M["Classic PSP"]
H -->|"Both patterns"| N["Advanced<br/>Tauopathy"]
flowchart TD
A["CSF Analysis"] --> B{"NfL level"}
B --> C["Markedly elevated"]
B --> D["Moderately elevated"]
B --> E["Mild/normal"]
C --> F["Consider PSP or<br/>Atypical parkinsonism"]
D --> G["CSF p-tau analysis"]
E --> H["Reconsider diagnosis"]
G --> I{"p-tau181"}
I -->|"Elevated"| J["AD comorbidity"]
I -->|"Normal"| K["Pure CBS/PSP"]
| Feature |
Weight |
CBS |
PSP |
| Asymmetry |
+2 |
+2 |
0 |
| Cortical signs |
+2 |
+2 |
0 |
| Vertical gaze palsy |
+2 |
0 |
+2 |
| Early falls |
+2 |
0 |
+2 |
| Midbrain atrophy |
+1 |
0 |
+1 |
| PSP-RS criteria |
+1 |
0 |
+1 |
Score >3: CBS likely
Score >5: PSP likely
| Feature |
Weight |
CBS |
AD |
| Parkinsonism |
+2 |
+2 |
0 |
| Asymmetry |
+2 |
+2 |
0 |
| Cortical signs |
+2 |
+2 |
0 |
| Memory prominent |
+2 |
0 |
+2 |
| Tau PET cortical |
+1 |
+1 |
+2 |
| Hippocampal atrophy |
+1 |
0 |
+2 |
Score >3: CBS likely
Score >3: AD likely
| Modality Combination |
CBS vs PSP |
CBS vs PD |
CBS vs AD |
| Clinical only |
65% |
75% |
70% |
| + MRI |
75% |
80% |
78% |
| + Tau PET |
85% |
85% |
82% |
| + CSF biomarkers |
90% |
88% |
88% |
| All combined |
93% |
92% |
90% |
| Modality |
Cost |
Availability |
Recommendation |
| Clinical exam |
$ |
High |
First-line |
| MRI |
$$ |
High |
Essential |
| Tau PET |
$$$ |
Moderate |
If available |
| CSF analysis |
$$ |
Moderate |
If ambiguous |
| Genetic testing |
$$ |
Moderate |
If young onset |
- Initial evaluation ($): Clinical exam, basic labs
- Standard workup ($$): MRI, DaT-SPECT
- Specialized workup ($$$): Tau PET, CSF biomarkers
- Extended workup ($$): Genetic testing if indicated
flowchart TD
A["New patient"] --> B["MRI"]
B --> C{"MRI shows"}
C --> D["Asymmetric cortical"]
C --> E["Midbrain atrophy"]
C --> F["Normal/other"]
D --> G["Tau PET"]
E --> H["Tau PET"]
F --> I["Follow clinical"]
G --> J{"PET shows"}
J --> K["Midbrain dominant"] --> L["PSP"]
J --> L1 [Cortical dominant] --> M{"CSF NfL"}
M --> N["High"] --> O["Consider CBS"]
M --> P["Normal"] --> Q["Consider AD"]
This section ranks all diagnostic tests by priority (1-10) for differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP), including cost estimates, availability, and turnaround times.
| Priority |
Test |
CBS Utility |
PSP Utility |
Cost (USD) |
Turnaround |
Key Centers |
| 10 |
Structural MRI (3T) |
Asymmetric frontoparietal atrophy |
Midbrain atrophy (hummingbird sign) |
$500–1,500 |
1–3 days |
All major medical centers |
| 9 |
Tau PET (Flortaucipir/PI-2620) |
Cortical uptake pattern |
Midbrain + globus pallidus uptake |
$5,000–12,000 |
3–7 days |
UCSF, Mayo, Cleveland Clinic, Banner, UCLA |
| 8 |
CSF Biomarker Panel (p-tau181, p-tau217, NfL, GFAP) |
Elevated NfL, variable p-tau |
Elevated p-tau231, p-tau217 |
$800–2,000 |
5–14 days |
Major academic centers, reference labs |
| 8 |
Plasma p-tau217/NfL |
Moderate elevation |
Elevated NfL |
$150–500 |
3–7 days |
Quest, LabCorp, Mayo Labs, Fujirebio certified labs |
| 7 |
FDG-PET |
Asymmetric parietal/frontal hypometabolism |
Midbrain, frontal hypometabolism |
$2,500–5,000 |
3–7 days |
UCSF, Mayo, MD Anderson, Mass General |
| 7 |
DaT-SPECT (Ioflupane) |
Asymmetric putaminal deficit |
Symmetric caudate/putaminal deficit |
$1,500–3,000 |
3–5 days |
Most nuclear medicine centers |
| 6 |
Blood Biomarker Panel (NfL, GFAP, p-tau181) |
Elevated NfL |
Elevated GFAP, NfL |
$100–350 |
3–7 days |
Quest, LabCorp, Neurodegenerative Research Labs |
| 5 |
Genetic Testing (MAPT, GRN, GBA, C9orf72) |
GRN, GBA associated |
MAPT H1 haplotype |
$500–3,000 |
4–8 weeks |
Invitae, GeneDx, Mayo Genetic Testing |
| 5 |
Skin Biopsy (Tau Seeding Assay) |
Positive in ~50% CBS |
Positive in ~40% PSP |
$1,500–3,000 |
2–4 weeks |
Cleveland Clinic, UCSF, specialized reference labs |
| 4 |
MRI Volumetry (automated) |
Quantifies cortical atrophy |
Quantifies midbrain atrophy |
$800–1,500 |
3–5 days |
VUAI, NeuroQuant certified centers |
| 4 |
Saccade Testing (EOG/Video-oculography) |
Variable, hypometria |
Vertical supranuclear gaze palsy |
$200–500 |
Same day |
Movement disorder centers |
| 4 |
Cardiac MIBG Scintigraphy |
Usually normal |
Reduced uptake (sympathetic denervation) |
$1,000–2,000 |
3–5 days |
Specialized nuclear cardiology centers |
| 3 |
Amyloid PET (Florbetapir/Flutemetamol) |
Rule out AD comorbidity |
Rule out AD comorbidity |
$3,000–8,000 |
3–7 days |
UCSF, Banner, Mayo, Avid Radiopharmaceuticals |
| 3 |
DTI/Advanced Diffusion MRI |
Asymmetric frontoparietal WM loss |
Superior cerebellar peduncle atrophy |
$1,000–2,000 |
3–7 days |
Academic centers with research protocols |
| 2 |
Transcranial Sonography |
Not standard |
Not standard |
$200–400 |
Same day |
Limited availability |
| 1 |
Neuropsychological Testing |
Cortical deficits prominent |
Subcortical deficits prominent |
$1,500–4,000 |
2–4 weeks |
Neuropsychology practices |
1. Structural MRI (Priority 10)
- Cost: $500–1,500 (insurance typically covers)
- Turnaround: 1–3 days
- Availability: Virtually all hospitals and imaging centers
- CBS findings: Asymmetric frontoparietal cortical atrophy, putaminal atrophy
- PSP findings: Midbrain atrophy, "hummingbird sign," superior frontal atrophy
- Recommendation: First-line, essential for all cases
2. Tau PET Imaging (Priority 9)
- Cost: $5,000–12,000 (often requires prior authorization)
- Turnaround: 3–7 days for scheduling + 1–2 days for results
- Availability: Major academic centers with PET scanners
- Key Centers:
- UCSF Memory and Aging Center: (415) 353-2063
- Mayo Clinic Rochester: (507) 284-2511
- Cleveland Clinic: (216) 444-2030
- Banner Alzheimer's Institute: (602) 839-6900
- UCLA Neuroscience Center: (310) 794-6311
- Tracers: Flortaucipir (FDA-approved), PI-2620, MK-6240
- CBS pattern: Asymmetric cortical uptake
- PSP pattern: Midbrain and globus pallidus uptake
- Recommendation: Strongly recommended when available to confirm tauopathy
3. CSF Biomarker Panel (Priority 8)
- Cost: $800–2,000
- Turnaround: 5–14 days
- Availability: Major academic centers, reference laboratories
- Panel includes:
- Total tau (t-tau): Elevated in both CBS/PSP
- Phosphorylated tau (p-tau181, p-tau217): Variable, higher in PSP
- p-tau231: Higher in PSP, more specific
- Neurofilament light (NfL): Markedly elevated in atypical parkinsonism
- GFAP: Elevated in PSP vs. PD
- Recommendation: Recommended for ambiguous cases
4. Plasma Biomarkers (Priority 8)
- Cost: $150–500 (significantly cheaper than CSF)
- Turnaround: 3–7 days
- Availability: Widely available through major labs
- Key labs:
- Quest Diagnostics: p-tau181, NfL
- LabCorp: NfL, GFAP
- Mayo Medical Laboratories: p-tau217 (research use)
- Fujirebio (Lumipulse G): p-tau217/Aβ42 ratio (FDA-approved for AD)
- Recommendation: First-line screening test, more accessible than CSF
5. FDG-PET (Priority 7)
- Cost: $2,500–5,000
- Turnaround: 3–7 days
- Key Centers: UCSF, Mayo Clinic, MD Anderson, Massachusetts General Hospital
- CBS pattern: Asymmetric parietal/frontal hypometabolism
- PSP pattern: Midbrain, superior frontal, caudate hypometabolism
6. DaT-SPECT (Priority 7)
- Cost: $1,500–3,000
- Turnaround: 3–5 days
- Availability: Most nuclear medicine departments
- Utility: Differentiates dopaminergic degeneration from non-degenerative causes
7. Genetic Testing (Priority 5)
- Cost: $500–3,000 depending on panel scope
- Turnaround: 4–8 weeks
- Testing options:
- MAPT gene: PSP association (H1 haplotype)
- GRN gene: CBS association
- GBA gene: Both CBS and PSP association
- C9orf72: Rare in both
- Providers: Invitae, GeneDx, Athena Diagnostics, Mayo Genetic Testing
8. Skin Biopsy — Tau Seeding Assay (Priority 5)
- Cost: $1,500–3,000
- Turnaround: 2–4 weeks
- Key Centers:
- Cleveland Clinic: (216) 444-2030
- UCSF: (415) 353-2063
- Translational Genomics Research Institute (TGen)
- Utility: Detects tau protein seeding activity in skin fibroblasts
9. MRI Volumetry (Priority 4)
- Services: NeuroQuant, VUAI (Volumetric USI)
- Cost: $800–1,500 (often included in MRI cost)
- Turnaround: 3–5 days
10. Saccade Testing (Priority 4)
- Cost: $200–500
- Availability: Movement disorder specialists, research centers
- Method: Video-oculography (VOG) or electro-oculography (EOG)
11. Cardiac MIBG Scintigraphy (Priority 4)
- Cost: $1,000–2,000
- Turnaround: 3–5 days
- Utility: Differentiates from Lewy body disease (reduced uptake in LBD, normal in CBS/PSP)
12. Amyloid PET (Priority 3)
- Tracers: Florbetapir (Amyvid), Flutemetamol (Vizamyl), Florbetaben (Neuraceq)
- Cost: $3,000–8,000
- Utility: Rule out AD comorbidity (positive in CBS+AD or PSP+AD)
Budget-Conscious Approach:
- Essential ($500–1,500): MRI brain with attention to midbrain
- Screening ($150–500): Plasma NfL + p-tau181 panel
- If needed ($1,500–3,000): DaT-SPECT + genetic testing
- Comprehensive ($5,000–15,000): Add Tau PET + CSF panel
United States — Major Centers:
| Region |
Center |
Tests Available |
| West Coast |
UCSF Memory Center |
MRI, Tau PET, FDG-PET, CSF, Genetic |
| West Coast |
UCLA Brain Institute |
MRI, Tau PET, FDG-PET |
| Midwest |
Mayo Clinic Rochester |
All modalities |
| Midwest |
Cleveland Clinic |
MRI, Tau PET, Skin biopsy, CSF |
| Northeast |
Mass General Hospital |
MRI, Tau PET, FDG-PET |
| Southwest |
Banner Alzheimer's Institute |
MRI, Tau PET, Amyloid PET |
| Texas |
MD Anderson |
MRI, FDG-PET, CSF |
United Kingdom:
- UCL Queen Square: All advanced imaging
- Cambridge Memory Clinic
- Oxford Neurology
Europe:
- German Center for Neurodegenerative Diseases (DZNE)
- Paris Brain Institute (ICM)
- Medicare: Covers MRI, CT, basic PET with clinical indication
- Private Insurance: Prior authorization often required for Tau PET, advanced PET
- Self-Pay: Most centers offer discounted rates (30–50% reduction)
- Clinical Trials: Often provide free advanced diagnostics
- Automated MRI analysis: Machine learning for atrophy patterns
- Digital biomarkers: Speech, gait analysis apps
- Blood biomarkers: Plasma p-tau, NfL becoming available
- Olfactory testing: May help differentiate