Normal Albumin Level in CSF
The normal CSF protein level is less than 0.4 g/L (400 mg/L), with the CSF/serum albumin ratio (albumin quotient) being the preferred method to assess blood-CSF barrier function, with an upper reference limit of 6.8 for individuals under 45 years and 10.2 for those over 45 years. 1, 2
Standard Reference Values
CSF Protein Concentration
- Normal CSF total protein: <0.4 g/L (<400 mg/L) 1
- Age-dependent upper reference limits range from 530-690 mg/L (95th percentile) for ages 18-70 years 3
- These values are higher than traditionally recommended, which explains why blood-CSF barrier dysfunction has been historically over-reported 3
CSF/Serum Albumin Ratio (Albumin Quotient)
- This is the preferred method for detecting blood-CSF barrier dysfunction 1, 4
- Upper reference limit for age <45 years: 6.8 2
- Upper reference limit for age >45 years: 10.2 2
- Alternative age-adjusted formula: age/25 + 8 3
- The albumin quotient shows increasing variability after age 45, suggesting less stable blood-CSF barrier function in older individuals 2
Clinical Context and Interpretation
Why Albumin Quotient is Superior
- CSF albumin or total protein concentrations alone are less satisfactory than the albumin quotient 4
- The albumin quotient accounts for serum albumin levels, which can vary significantly between patients 5
- Approximately 41.9% of CSF albumin variation in normal patients is explained by barrier permeability, while 54.8% is explained by CSF flow 5
Important Technical Considerations
- CSF should be analyzed from the first 12 mL collected, as albumin concentration decreases by 21% between the first (0-4 mL) and last (21-24 mL) portions due to concentration gradients 6
- Results must be interpreted with reference to patient age and local laboratory methods 4
- Normal CSF cell count is ≤4 cells/μL 4
Pathological Elevations
- Bacterial meningitis: Protein typically >2.2 g/L (markedly raised); levels <0.6 g/L make bacterial disease very unlikely 1, 7
- Tuberculous meningitis: Markedly raised protein (often >1 g/L) 1
- Viral meningitis: Mildly raised protein 1
- Fungal meningitis: Raised protein 1
- Blood-CSF barrier disruption (vascular cognitive impairment, critical illness): Elevated albumin quotient indicates leakage across compromised barrier 1
Common Pitfalls to Avoid
- Do not interpret CSF glucose in isolation—always obtain simultaneous plasma glucose to calculate the CSF:plasma glucose ratio (normal >0.66) 1, 7
- Do not use outdated reference ranges—current evidence suggests higher upper limits than traditionally taught, reducing false-positive diagnoses of barrier dysfunction 3
- Do not analyze CSF from non-standardized volumes—protein concentrations vary significantly with collection volume 6
- Do not ignore age-related changes—barrier function becomes more variable after age 45, requiring adjusted reference ranges 2