Cerebrospinal fluid (CSF) biomarkers provide direct molecular insights into central nervous system pathology and are essential for differential diagnosis of neurodegenerative diseases. This page compares key CSF biomarkers across Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD)[1][2].
| Biomarker | AD | PD | ALS | FTD |
|---|---|---|---|---|
| t-Tau | ↑↑ | ↔/↑ | ↑ | ↔/↑ |
| p-Tau181 | ↑↑ | ↔ | ↔ | ↔ |
| p-Tau217 | ↑↑ | ↔ | ↔ | ↔ |
| p-Tau231 | ↑ | ↔ | ↔ | ↔ |
| Biomarker | AD | PD | ALS | FTD |
|---|---|---|---|---|
| NfL | ↑ | ↔/↑ | ↑↑↑ | ↑/↑↑ |
| NfH | ↑ | ↔/↑ | ↑↑↑ | ↑ |
| Biomarker | AD | PD | ALS | FTD |
|---|---|---|---|---|
| Total α-syn | ↓ | ↓↓ | ↔ | ↔ |
| RT-QuIC PD | - | + | - | - |
| TDP-43 | ↔ | ↔ | ↑↑ | ↑ |
Key biomarker profile: ↓ Aβ42/Aβ40 + ↑ p-tau181/217 + ↑ t-tau
Key biomarker profile: ↓ total α-syn + normal p-tau/t-tau
Key biomarker profile: ↑↑ NfL + ↑ TDP-43
Key biomarker profile: ↑ NfL + normal AD biomarkers
| Biomarker | AD | PD | ALS | FTD |
|---|---|---|---|---|
| Aβ42/Aβ40 | ↓↓ | ↔ | ↔ | ↔ |
| p-Tau181 | ↑↑ | ↔ | ↔ | ↔ |
| p-Tau217 | ↑↑ | ↔ | ↔ | ↔ |
| t-Tau | ↑↑ | ↔/↑ | ↑ | ↔/↑ |
| NfL | ↑ | ↔/↑ | ↑↑↑ | ↑/↑↑ |
| α-syn (total) | ↓ | ↓↓ | ↔ | ↔ |
| TDP-43 | ↔ | ↔ | ↑↑ | ↑ |
| GFAP | ↑ | ↔ | ↑ | ↔/↑ |
| Neurogranin | ↑↑ | ↑ | ↑ | ↔/↑ |
Assay variability: Different platforms have different cutoffs
Overlap: Biomarkers can be elevated in multiple conditions
Sensitivity/specificity: No single biomarker is pathognomonic
Dynamic range: Some biomarkers have ceiling effects
Blennow K, et al. Cerebrospinal fluid biomarker analysis: recent updates and recommendations for Alzheimer's disease. Mol Neurodegener. 2020. ↩︎
Simonsen AH, et al. CSF biomarkers in neurodegenerative diseases: clinical utility and approach. Nat Rev Neurol. 2022. ↩︎
Hansson O, et al. CSF biomarkers vs FDG-PET: Agreement and prognostic value in the Swedish BioFINDER study. Alzheimers Dement. 2022. ↩︎
Palmqvist S, et al. Discriminative accuracy of plasma p-tau217 for Alzheimer disease across the cognitive continuum. JAMA Neurol. 2021. ↩︎
Janelidze S, et al. CSF p-tau231 performs better than p-tau181 and p-tau217 in discriminating AD from other neurodegenerative diseases. Nat Commun. 2020. ↩︎
Schindler SE, et al. Combining cerebrospinal fluid biomarkers with brain amyloid PET for differential diagnosis of dementia. JAMA Neurol. 2022. ↩︎
Benatar M, et al. Neurofilament light chain in blood and CSF as a biomarker in ALS. Nat Rev Neurol. 2022. ↩︎ ↩︎
Parnetti L, et al. Cerebrospinal fluid biomarkers in Parkinson's disease: from the limbic system to the brain. Brain. 2019. ↩︎
Kasai T, et al. TDP-43 in cerebrospinal fluid of patients with ALS and FTLD: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2020. ↩︎
Lista S, et al. Neurogranin in cerebrospinal fluid and blood as a biomarker of synaptic dysfunction. JAMA Neurol. 2015. ↩︎
Blennow K, et al. Lecanemab: the beginning of the end of Alzheimer's disease?. Nat Rev Neurol. 2023. ↩︎