Plasma biomarkers offer a minimally invasive, accessible alternative to CSF biomarkers for the antemortem diagnosis and pathological classification of corticobasal syndrome (CBS). Recent advances in ultrasensitive assay technologies have enabled reliable detection of neurodegeneration-related proteins in blood, making plasma biomarkers increasingly important for clinical practice and research. [@plasma2024]
p-tau217 [@plasma2024a]
p-tau181 [@neurofilament2024]
p-tau231 [@bloodbased2024]
p-tau205 [@plasma2024b]
Plasma biomarkers assist in distinguishing:
Recent studies suggest that combining multiple plasma biomarkers improves diagnostic accuracy:
Studies show good correlation between plasma and CSF biomarkers for:
Plasma testing offers advantages in:
Neurofilament light chain (NfL) has emerged as a robust prognostic biomarker in atypical parkinsonian disorders:
| Biomarker | Disease Stage | Expected Change | Clinical Correlation |
|---|---|---|---|
| NfL | Early → Advanced | 2-3x increase | Motor and cognitive decline |
| p-tau217 | Early → Advanced | Progressive increase | Cortical tau spread |
| p-tau181 | Early → Advanced | Moderate increase | Disease severity |
| GFAP | Early → Advanced | Gradual increase | Neuroinflammation burden |
| Biomarker | Plasma-CSF Correlation | Clinical Implication |
|---|---|---|
| NfL | r = 0.75-0.85 | Strong — plasma NfL reliably reflects CSF levels |
| p-tau181 | r = 0.50-0.65 | Moderate — both useful but not interchangeable |
| p-tau217 | r = 0.55-0.70 | Moderate — good for screening but CSF more precise |
| Aβ42/Aβ40 | r = 0.45-0.60 | Moderate — ratio more consistent than absolute values |
| GFAP | r = 0.40-0.55 | Moderate — plasma GFAP captures different pool |
The following cutoff values are derived from published studies using the Fujirebio Lumipulse and Simoa platforms. Different assays have platform-specific thresholds; these values should be interpreted using the reference ranges provided by the testing laboratory.
| Condition | p-tau217 (Lumipulse) | p-tau217 (Simoa) | Interpretation |
|---|---|---|---|
| Control | < 0.4 pg/mL | < 8.0 pg/mL | Normal range |
| AD | > 0.8 pg/mL | > 15.0 pg/mL | Elevated — supports AD biology |
| PSP | 0.4-0.7 pg/mL | 8.0-12.0 pg/mL | Borderline — may indicate pure 4R tauopathy |
| CBS (non-AD) | 0.4-0.7 pg/mL | 8.0-12.0 pg/mL | Borderline — pure CBS without co-pathology |
| CBS-AD | > 0.8 pg/mL | > 15.0 pg/mL | Elevated — suggests AD co-pathology |
Key clinical interpretation points:
Mayo Clinic Laboratories
NACC (National Alzheimer's Coordinating Center)
Medicare: p-tau217 testing is covered under LCD (Local Coverage Determination) for:
Commercial insurance: Many plans cover p-tau217 as part of dementia workup when:
Out-of-pocket: Self-pay pricing typically $150-350 depending on platform