From the Department of Human Neurosciences (B.O., A.M., E.C.I., M.S.B., E.M.S., A.T.G., C.D.B.), "Sapienza" University of Rome; Fondazione European Brain Research Institute (EBRI) Rita Levi-Montalcini (V.M., C.D.A., I.A., M.D.O.) Department of Neurosciences (C.V., P.P.), Istituto Superiore di Sanità, Rome; Department of Odontostomatological and Maxillofacial Sciences (E.M.), "Sapienza" University of Rome; Department of Clinical Internal (S.G.), Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome; Department of Physiology and Pharmacology (G.R.), Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy; and Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Raffaele Roma (G.R.).
Neurology. 2023 Nov 7;101(19):e1933-e1938. doi: 10.1212/WNL.0000000000207799. Epub 2023 Aug 31.
Different pathophysiologic mechanisms, especially involving astrocytes, could contribute to tuberous sclerosis complex (TSC). We assessed neurodegeneration and astrocytopathy plasma biomarkers in adult patients with TSC to define TSC biomarker profile and investigate clinical-radiologic correlations.
Patients with TSC aged 15 years or older 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 (HCs): tTau, pTau181, Abeta, Abeta, neurofilament light chain, and glial fibrillary acid protein (GFAP).
Thirty-one patients (20 females/11 males; median age 30 years, interquartile range 24-47) and 38 HCs were enrolled. Only GFAP was significantly higher in the whole TSC population than in HCs (132.71 [86.14-231.06] vs 44.80 [32.87-66.76] pg/mL, < 0.001), regardless of genotype. GFAP correlated with the disease clinical (ρ = 0.498, = 0.005) and radiologic severity (ρ = 0.417, = 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, < 0.0001), moderate-severe intellectual disability (200.80 [78.40-427.6] vs 105.08 [46.80-152.58] pg/mL, = 0.040), and autism spectrum disorder (306.26 [159.07-584.47] vs 109.34 [72.56-152.08] pg/mL, = 0.021).
Our exploratory study documented a significant increase of GFAP plasma concentration in adult patients with TSC, correlated with their neurologic severity, supporting the central role of astrocytopathy in TSC pathophysiology.
不同的病理生理机制，特别是涉及星形胶质细胞的机制，可能导致结节性硬化症（TSC）。我们评估了成年 TSC 患者的神经退行性变和星形胶质细胞病变的血浆生物标志物，以确定 TSC 生物标志物特征，并研究临床-影像学相关性。
2021 年 7 月至 2022 年 6 月，连续招募在罗马“Umberto I”综合医院就诊的年龄在 15 岁及以上的 TSC 患者。比较 TSC 患者与年龄/性别匹配的健康对照者（HCs）的以下生物标志物血浆水平：总 Tau（tTau）、磷酸化 Tau181（pTau181）、β-淀粉样蛋白（Abeta）、总 Abeta、神经丝轻链和胶质纤维酸性蛋白（GFAP）。
共纳入 31 例患者（20 例女性/11 例男性；中位年龄 30 岁，四分位间距 24-47）和 38 例 HCs。整个 TSC 患者群体的 GFAP 明显高于 HCs（132.71[86.14-231.06]比 44.80[32.87-66.76]pg/ml，<0.001），无论基因型如何。GFAP 与疾病的临床严重程度（ρ=0.498，=0.005）和影像学严重程度（ρ=0.417，=0.001）相关。在伴有癫痫性痉挛（254.50[137.54-432.96]比 86.92[47.09-112.76]pg/ml，<0.0001）、中度-重度智力障碍（200.80[78.40-427.6]比 105.08[46.80-152.58]pg/ml，=0.040）和自闭症谱系障碍（306.26[159.07-584.47]比 109.34[72.56-152.08]pg/ml，=0.021）的患者中，GFAP 明显升高。
我们的探索性研究记录了成年 TSC 患者 GFAP 血浆浓度的显著增加，与他们的神经严重程度相关，支持星形胶质细胞病变在 TSC 病理生理学中的核心作用。
