Differences in Neurofilament Light Chain, Glial Fibrillary Acidic Protein, and Tau Protein Levels in Patients with Temporal Lobe Epilepsy and Comorbid Depression.

This study aimed to compare plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau 181 (p-Tau181), and phosphorylated tau 217 (p-Tau217) among patients with temporal lobe epilepsy with comorbid depression (TLE-D), patients with temporal lobe epilepsy alone (TLE), and the healthy control group (HC), and to examine the associations of these biomarkers with clinical characteristics and depressive symptoms. A total of 28 patients in the TLE-D group, 43 patients in the TLE group, and 29 participants in the HC group were recruited between March 2023 and July 2025. Plasma biomarker levels were measured using chemiluminescent immunoassay (CLIA), and depressive symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17). Group differences were analyzed using the chi-square test, one-way analysis of variance, Kruskal-Wallis H test, and Mann-Whitney U test. Generalized linear models (GLMs) were used to examine independent associations. In the first step, demographic variables, including body mass index (BMI), age, and sex, were entered; in the second step, clinical variables, including temporal lobe lesions and seizure frequency, were additionally included. No significant differences were observed among the three groups in sex (P = 0.181), age (P = 0.394), or BMI (P = 0.319). HAMD-17 scores were significantly higher in the TLE-D group than in the TLE and HC groups (P < 0.001), whereas seizure frequency (P = 0.607) and temporal lobe lesions (P = 0.239) did not differ significantly between the two epilepsy groups. In the overall sample, plasma GFAP levels were highest in the TLE-D group, intermediate in the TLE group, and lowest in the HC group, with age identified as a significant covariate (B = 0.007, P = 0.035). In the second-step analysis restricted to the two epilepsy groups, GFAP levels remained significantly higher in the TLE-D group than in the TLE group (P = 0.005). For NfL, both the TLE-D and TLE groups showed higher levels than the HC group (both FDR-corrected P values were 0.0015), whereas no significant difference was observed between the TLE-D and TLE groups (FDR-corrected P = 0.277). In the second-step analysis restricted to the two epilepsy groups, seizure frequency was negatively associated with NfL levels (B = -0.242, P = 0.005). In the overall sample, plasma p-Tau181 levels were higher in the TLE-D group than in both the TLE and HC groups (both FDR-corrected P values were 0.024), whereas no significant difference was found between the TLE and HC groups (FDR-corrected P = 0.992). In the second-step analysis restricted to the two epilepsy groups, p-Tau181 levels remained significantly higher in the TLE-D group than in the TLE group (P = 0.014). Plasma p-Tau217 levels were also higher in the TLE-D group than in both the TLE and HC groups (both FDR-corrected P values were 0.002). Sex was a significant covariate (B = 0.411, P < 0.001), with females showing higher p-Tau217 levels than males, and BMI was negatively associated with p-Tau217 levels (B = -0.051, P = 0.022). In the second-step analysis restricted to the two epilepsy groups, p-Tau217 levels remained significantly higher in the TLE-D group than in the TLE group (P = 0.002). Sex was also associated with p-Tau217 levels, with higher levels observed in females than in males (B = 0.526, P < 0.001). BMI and seizure frequency were both negatively associated with p-Tau217 levels (B = -0.073, P = 0.017; B = -0.090, P = 0.032). These findings suggest that GFAP, NfL, and tau-related proteins may be associated with depression comorbidity in temporal lobe epilepsy and may provide clues for future studies on the underlying biological mechanisms and their potential clinical relevance.