Cerebrospinal Fluid Biomarkers in Neurodegenerative Conditions

Cerebrospinal fluid (CSF) biomarkers have become indispensable tools in the diagnosis, monitoring and mechanistic understanding of neurodegenerative diseases. By analysing proteins, peptides and other molecular constituents in the fluid that surrounds the brain and spinal cord, researchers can infer processes of neuronal injury, synaptic dysfunction and glial activation. Key biomarkers such as amyloid beta, tau species and neurofilament light reflect central pathologies of Alzheimer’s disease, Parkinson’s disease and related disorders. Recent advances have refined assay sensitivity and specificity, enabled multiplex measurement of synaptic and inflammatory markers, and uncovered novel indicators of synaptic plasticity and neuroinflammation. Together, these developments inform both clinical decision-making and the evaluation of emerging therapies, underscoring the global significance of CSF biomarker research in neurodegeneration.

Research from Nature Portfolio

In Alzheimer’s disease, elevated levels of growth-associated protein 43 (GAP-43) in CSF have been linked to accelerated amyloid-beta-driven tau accumulation and trans-synaptic spread. Longitudinal imaging studies combined with fluid measurements demonstrate that higher GAP-43 concentrations correlate with more rapid tau propagation along anatomically connected regions. These findings highlight synaptic dysfunction as a key mediator of tau pathology and suggest that synaptic biomarkers such as GAP-43 could serve as targets for interventions aimed at halting disease progression.

Cerebrospinal Fluid Biomarkers in Neurodegenerative Conditions publication trend

The graph below shows the total number of articles in cerebrospinal fluid biomarkers in neurodegenerative conditions across all publications each year (not limited to Nature Index journals).

Technical terms

Cerebrospinal fluid (CSF): The clear fluid surrounding the brain and spinal cord, used to assess central nervous system biomarkers.

Amyloid beta (Aβ): A peptide that aggregates into plaques in Alzheimer’s disease, detectable in fluid as Aβ42 and Aβ40 species.

Tau phosphorylation (p-tau): Modification of tau protein by phosphate groups, associated with neurofibrillary tangle formation in Alzheimer’s disease.

Neurofilament light (NfL): A cytoskeletal protein released during axonal injury, serving as a marker of neurodegeneration.

Neurogranin (Ng): A postsynaptic protein involved in synaptic plasticity, elevated in fluid during synaptic degeneration.

Glial fibrillary acidic protein (GFAP): An astrocytic intermediate filament protein, reflecting astroglial activation and neuroinflammation.

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2): A microglial receptor fragment in fluid, indicative of microglial activation.

References

1. Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer’s disease. Nature Communications (2024).
2. Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease. JAMA Neurology (2024).
3. CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration. Molecular Neurodegeneration (2024).
4. Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease. EMBO Molecular Medicine (2016).