Establishing Neuron-Specific Enolase Reference Intervals: A Comparative Analysis of Partitioned Approach- and Gender-Based Continuous Age- and Season-Related Models

<b>Background/Objectives</b>: Static reference intervals (RIs) fail to capture the dynamic changes in bioanalytes. This study aimed to develop gender-based continuous age- and season-related RIs for neuron-specific enolase (NSE) using real-world data and to compare them with partitioned RIs. <b>Methods:</b> The NSE results from 4097 individuals were included after rigorous screening. Partitioned RIs were determined using the Hoffmann method. Generalized additive models for location, scale and shape (GAMLSS) were selected to develop continuous RIs. <b>Results:</b> The partitioned RIs are as follows: <16.4 µg/L for males aged ≥19 years; <14.47 µg/L for females aged 19-49 years; and <17.25 µg/L for females aged ≥50 years. For continuous RIs, NSE levels in males remain stable with age, while in females, NSE levels evidently increase around the age of 50. Although less impactful than age, seasonal changes still affect NSE levels. Dynamic changes and continuous RIs for NSE are visualized in this study. <b>Conclusions:</b> We developed gender-based continuous age- and season-integrated RIs for NSE in North China, highlighting the variation in NSE levels in females with age and season. Compared to static RIs, continuous RIs are more responsive to NSE, potentially enhancing the precision and individualization of health assessments.