Plasma biomarker profile and clinical correlations in adult patients with tuberous sclerosis complex

Background and objectives: Different pathophysiological mechanisms, especially involving astrocytes, could contribute to Tuberous Sclerosis Complex (TSC). We assessed neurodegeneration and astrocytopathy plasma biomarkers in TSC adult patients to define TSC biomarker profile and investigate clinical-radiological correlations. Methods: TSC patients≥15 years followed at Policlinico "Umberto I" of Rome were consecutively enrolled (July 2021-June 2022). The plasma levels of the following biomarkers were compared between patients and age/sex-matched healthy controls (HC): tTau, pTau181, Abeta40, Abeta42, Neurofilament Light Chain, Glial Fibrillary Acid Protein (GFAP). Results: Thirty-one patients (20 females/11 males; median age 30 years, IQR 24-47) and 38 HC were enrolled. Only GFAP was significantly higher in the whole TSC population than in HC [132.71 (86.14-231.06) vs 44.80 (32.87-66.76) pg/mL, p<0.001], regardless of genotype. GFAP correlated with the disease clinical (ρ=0.498, p=0.005) and radiological severity (ρ=0.417, p=0.001). It was significantly higher in patients with epileptic spasms [254.50 (137.54-432.96) vs 86.92 (47.09-112.76) pg/mL, p<0.0001], moderate-severe intellectual disability [200.80 (78.40-427.6) vs 105.08 (46.80-152.58) pg/mL, p=0.040] and autism spectrum disorder [306.26 (159.07-584.47) vs 109.34 (72.56-152.08) pg/mL, p=0.021]. Discussion: Our exploratory study documented a significant increase of GFAP plasma concentration in TSC adult patients, correlated with their neurological severity, supporting the central role of astrocytopathy in TSC pathophysiology.