Age-stratified reference intervals for cerebrospinal fluid total protein in adults undergoing lumbar puncture: A 19-year retrospective study

Using 19 years of retrospective clinical data, we estimated age-stratified reference intervals for cerebrospinal fluid total protein (CSF-TP) in a selected reference-like subset of Chinese adults undergoing diagnostic lumbar puncture. We also examined factors associated with CSF-TP concentrations. A retrospective analysis was conducted using 29,519 CSF-TP test records from patients who underwent lumbar puncture at Zhongshan City People's Hospital between 2006 and 2025. Of these, 4217 records met the basic age and laboratory criteria; after structured chart review of the clinical history, 253 candidate cases remained. After 2 statistically identified outliers were removed, 251 cases were included. Nonparametric methods were used to estimate CSF-TP reference intervals (P2.5-P97.5) for the overall sample and the 2 age groups, and 90% confidence intervals were estimated using bootstrap resampling. Sex-stratified estimates were considered exploratory. The overall reference interval for CSF-TP in the study population was 18.13 to 73.33 mg/dL. When stratified by age, individuals aged 18 to 48 years had a reference interval of 17.15 to 55.37 mg/dL, while those aged 49 to 85 years had a higher interval of 21.85 to 80.51 mg/dL. A positive correlation was observed between CSF-TP concentration and age (Spearman's ρ = 0.35, P < .001). The median CSF-TP in the 49- to 85-year-old group was 40.9 mg/dL, which was 19.2% higher than the median of 34.3 mg/dL in the 18- to 48-year-old group. In addition, a significant sex difference was found: males had a median CSF-TP of 38.7 mg/dL, which was higher than the median of 34.2 mg/dL observed in females (P < .001). Statistically significant associations were also found between CSF-TP and cerebrospinal fluid white blood cell and red blood cell counts, but their explanatory power was limited (white blood cell: Pearson r = 0.1684, r2 = 0.0284; red blood cell: Pearson r = 0.1293, r2 = 0.0167). In this single-center reference-like subset of adults undergoing diagnostic lumbar puncture, CSF-TP increased with age. The age-related reference intervals estimated in this study require direct-method validation and may assist the interpretation of CSF-TP results in similar clinical populations.