The Neurodegenerative Biomarker Correlation Matrix provides a comprehensive comparison of cerebrospinal fluid (CSF) and blood-based biomarkers across major neurodegenerative diseases. This matrix enables clinicians and researchers to understand biomarker patterns for differential diagnosis and disease progression monitoring. [1]
This page synthesizes evidence from the latest biomarker studies across Alzheimer's disease (AD), Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA), Frontotemporal Dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS)[@blennow2024][@hansson2024]. [2]
| Symbol | Meaning | [3]
|--------|---------| [4]
| ↑↑ | Strongly elevated | [5]
| ↑ | Moderately elevated | [6]
| ↔ | Normal | [7]
| ↓ | Moderately decreased | [8]
| ↓↓ | Strongly decreased | [9]
| Biomarker | AD | PD | DLB | MSA | FTD | ALS | [10]
|-----------|-----|------|------|------|------|------| [11]
| p-tau181 | ↑↑ | ↔ | ↔/↑ | ↔ | ↔ | ↔ | [12]
| p-tau217 | ↑↑ | ↔ | ↔/↑ | ↔ | ↔ | ↔ |
| NfL | ↑ | ↔/↑ | ↑ | ↑↑ | ↑/↑↑ | ↑↑↑ |
| Alpha-synuclein | ↓ | ↓↓ | ↓↓ | ↓↓ | ↔ | ↔ |
| TDP-43 | ↔ | ↔ | ↔ | ↔ | ↑ | ↑↑ |
| GFAP | ↑ | ↔ | ↔/↑ | ↔/↑ | ↔/↑ | ↑ |
| Biomarker | AD | PD | DLB | MSA | FTD | ALS |
|---|---|---|---|---|---|---|
| p-tau181 | ↑↑ | ↔ | ↔ | ↔ | ↔ | ↔ |
| p-tau217 | ↑↑ | ↔ | ↔ | ↔ | ↔ | ↔ |
| NfL | ↑ | ↔/↑ | ↑ | ↑↑ | ↑ | ↑↑↑ |
| Alpha-synuclein | ↔ | ↓/↔ | ↓/↔ | ↓ | ↔ | ↔ |
| TDP-43 | ↔ | ↔ | ↔ | ↔ | ↑ | ↑ |
| GFAP | ↑↑ | ↔ | ↔/↑ | ↔ | ↔/↑ | ↑ |
Best for: Distinguishing AD from other neurodegenerative diseases
| Metric | AD vs. Controls | AD vs. FTD | AD vs. PD |
|---|---|---|---|
| Sensitivity | 85-90% | 85% | 90% |
| Specificity | 85-90% | 80% | 88% |
| AUC | 0.92-0.95 | 0.88 | 0.93 |
Best for: Highest accuracy for AD across the cognitive continuum
| Metric | AD vs. Controls | AD vs. FTD | AD vs. DLB |
|---|---|---|---|
| Sensitivity | 88-92% | 90% | 88% |
| Specificity | 88-92% | 85% | 82% |
| AUC | 0.94-0.97 | 0.91 | 0.88 |
Best for: General neurodegeneration marker, prognostic utility
| Metric | ALS vs. Controls | ALS vs. FTD | PD vs. MSA |
|---|---|---|---|
| Sensitivity | 90-95% | 85% | 75% |
| Specificity | 90-95% | 80% | 82% |
| AUC | 0.96-0.98 | 0.88 | 0.82 |
Best for: Detecting synucleinopathies (PD, DLB, MSA)
| Metric | PD vs. Controls | DLB vs. AD | MSA vs. PD |
|---|---|---|---|
| Sensitivity (RT-QuIC) | 88-95% | 75% | 80% |
| Specificity (RT-QuIC) | 90-95% | 82% | 78% |
| AUC | 0.92 | 0.80 | 0.81 |
Best for: Detecting TDP-43 proteinopathies (ALS, FTD)
| Metric | ALS vs. Controls | FTD vs. AD | ALS-FTD vs. PD |
|---|---|---|---|
| Sensitivity | 70-80% | 75% | 78% |
| Specificity | 80-85% | 78% | 82% |
| AUC | 0.82 | 0.80 | 0.84 |
Best for: Astrocyte activation, AD-specific elevation in blood
| Metric | AD vs. Controls | AD vs. FTD | AD vs. PD |
|---|---|---|---|
| Sensitivity | 80-85% | 78% | 85% |
| Specificity | 82-88% | 75% | 88% |
| AUC | 0.88-0.92 | 0.82 | 0.90 |
Core biomarker signature: ↓ Aβ42/Aβ40 + ↑↑ p-tau181/217 + ↑ NfL + ↑ GFAP
| Biomarker | CSF | Blood | Clinical Utility |
|---|---|---|---|
| Aβ42/Aβ40 | ↓↓ | ↓ | Amyloid pathology detection |
| p-tau181 | ↑↑ | ↑↑ | Core diagnostic marker |
| p-tau217 | ↑↑ | ↑↑ | Highest accuracy |
| NfL | ↑ | ↑ | Disease progression |
| GFAP | ↑ | ↑↑ | Astrocyte activation |
Core biomarker signature: ↓ total α-syn + RT-QuIC positive + normal tau
| Biomarker | CSF | Blood | Clinical Utility |
|---|---|---|---|
| Total α-syn | ↓↓ | ↓/↔ | Synuclein pathology |
| p-Ser129 α-syn | ↑ | ↑ | Pathology burden |
| NfL | ↔/↑ | ↔/↑ | Cognitive decline risk |
| RT-QuIC | + (88-95%) | N/A | Disease confirmation |
Core biomarker signature: ↓ α-syn + normal tau + ↑ NfL
| Biomarker | CSF | Blood | Clinical Utility |
|---|---|---|---|
| Total α-syn | ↓↓ | ↓/↔ | Synuclein pathology |
| p-tau181 | ↔/↑ | ↔ | AD comorbidity |
| NfL | ↑ | ↑ | Disease severity |
| RT-QuIC | + (75-85%) | N/A | DLB confirmation |
Core biomarker signature: ↓ α-syn + ↑↑ NfL + normal tau
| Biomarker | CSF | Blood | Clinical Utility |
|---|---|---|---|
| Total α-syn | ↓↓ | ↓ | Synuclein pathology |
| NfL | ↑↑ | ↑↑ | Distinguish from PD |
| p-tau | ↔ | ↔ | Rule out AD |
| RT-QuIC | + (80-90%) | N/A | MSA confirmation |
Core biomarker signature: ↑ NfL + normal AD biomarkers + ↑ TDP-43
| Biomarker | CSF | Blood | Clinical Utility |
|---|---|---|---|
| NfL | ↑/↑↑ | ↑ | Disease severity |
| p-tau | ↔ | ↔ | Rule out AD |
| TDP-43 | ↑ | ↑ | FTD-FUS/ALS-FTD |
| Progranulin | ↓ (genetic) | ↓ (genetic) | Genetic subtype |
Core biomarker signature: ↑↑ NfL + ↑ TDP-43 + normal tau
| Biomarker | CSF | Blood | Clinical Utility |
|---|---|---|---|
| NfL | ↑↑↑ | ↑↑↑ | Diagnostic + prognostic |
| pNfH | ↑↑ | ↑↑ | Disease progression |
| TDP-43 | ↑↑ | ↑ | Pathology burden |
| p-tau | ↔ | ↔ | Rule out AD |
| Panel | AD | FTD | ALS |
|---|---|---|---|
| p-tau181 | ↑↑ | ↔ | ↔ |
| p-tau217 | ↑↑ | ↔ | ↔ |
| NfL | ↑ | ↑/↑↑ | ↑↑↑ |
| TDP-43 | ↔ | ↑ | ↑↑ |
Algorithm: If p-tau elevated → AD. If NfL very high with TDP-43 → ALS. If NfL elevated with normal p-tau and TDP-43 → FTD.
| Panel | PD | DLB | MSA |
|---|---|---|---|
| α-syn (total) | ↓↓ | ↓↓ | ↓↓ |
| NfL | ↔/↑ | ↑ | ↑↑ |
| RT-QuIC | + | + | + |
| p-tau | ↔ | ↔/↑ | ↔ |
Algorithm: If NfL very high → MSA. If NfL moderately elevated with cognitive fluctuations → DLB. If NfL normal/mildly elevated → PD.
| Panel | AD | DLB | PD |
|---|---|---|---|
| p-tau181/217 | ↑↑ | ↔/↑ | ↔ |
| α-syn | ↓ | ↓↓ | ↓↓ |
| NfL | ↑ | ↑ | ↔/↑ |
| GFAP | ↑↑ | ↔/↑ | ↔ |
Step 1: Test p-tau181 or p-tau217
Step 2: Test α-synuclein RT-QuIC
Step 3: Test NfL and TDP-43
Blennow K, et al, The global blood-based biomarker market in neurodegeneration (2024) ↩︎
Hansson O, et al, Blood biomarkers for differential diagnosis and prognosis (2024) ↩︎
Zetterberg H, et al, Biomarker-based classification of neurodegenerative diseases (2024) ↩︎
Pichet Bin C, et al, Comparative performance of plasma p-tau217 and p-tau181 (2024) ↩︎
Thijssen EH, et al, Plasma p-tau217 and p-tau181 discriminate AD (2024) ↩︎
Kaufmann L, et al, Neurofilament light chain as biomarker for ALS (2024) ↩︎
Oroza M, et al, Alpha-synuclein seed amplification assay in PD (2024) ↩︎
Leotti TB, et al, TDP-43 in CSF for ALS-FTD spectrum (2024) ↩︎
Garton T, et al, GFAP as biomarker for neurodegeneration (2024) ↩︎
Singer M, et al, MSA versus PD: fluid biomarker differentiation (2024) ↩︎
Irina S, et al, DLB versus AD: CSF and blood biomarker discriminative accuracy (2024) ↩︎
Vansteene D, et al, FTD subtypes differentiation using CSF NfL and p-tau (2024) ↩︎