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Decoding the CSF Proteomic Signature of Idiopathic Normal Pressure Hydrocephalus: A Systematic Review
Aleksandra Kwiecień1, Małgorzata Dudzic1, Andrzej Lemański2
1Department of Neurology, Municipal Hospital in Poznań, 3 Szwajcarska Street, 61-285 Poznań, Poland.
Molecules (Basel, Switzerland)
|July 15, 2026
Summary
Idiopathic normal pressure hydrocephalus (iNPH) shows altered cerebrospinal fluid (CSF) proteins, with potential for diagnosing the condition and predicting shunt response. Further validation is needed for these candidate biomarkers.
Area of Science:
- Neurology
- Proteomics
- Biomarker Discovery
Background:
- Idiopathic normal pressure hydrocephalus (iNPH) presents diagnostic challenges, particularly in predicting shunt responsiveness.
- Cerebrospinal fluid (CSF) proteomic analysis offers a potential avenue for identifying diagnostic and prognostic biomarkers in iNPH.
Purpose of the Study:
- To systematically review and synthesize evidence on CSF proteomic biomarkers in iNPH.
- To identify molecular patterns relevant for iNPH diagnosis and predicting response to shunting procedures.
Main Methods:
- A PRISMA-guided systematic literature search was conducted across PubMed, Web of Science, and Google Scholar.
- Included 14 studies with 1171 iNPH patients, analyzing proteomic data from CSF.
- Focused on identifying consistent protein expression patterns and their association with iNPH.
Main Results:
- Consistent proteomic patterns in iNPH include upregulated inflammatory and extracellular matrix proteins, and downregulated synaptic/neuronal markers.
- Neurodegenerative proteins (amyloid-β, tau, NFL) showed potential in differentiating iNPH from other neurodegenerative diseases and predicting shunt response.
- Substantial heterogeneity exists across studies, with identified proteins currently considered candidate biomarkers.
Conclusions:
- CSF proteomic profiles suggest a multifactorial iNPH model involving impaired clearance, neuroinflammation, and axonal stress.
- Multidimensional biomarker panels, rather than single proteins, may offer greater clinical utility but require validation.
- A conceptual iNPH proteomic "Vulnerability Model" is proposed, needing rigorous validation for clinical application in patient stratification and outcome prediction.
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