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.

Plasma biomarker profile and clinical correlations in adult patients with tuberous sclerosis complex / Orlando, Biagio; Morano, Alessandra; Manzini, Valeria; CERULLI IRELLI, Emanuele; S Borioni, Maria; Veroni, Caterina; Salamone, ENRICO MICHELE; D'Amelio, Chiara; Moliterni, Elisa; Giustini, Sandra; Ruffolo, Gabriele; Arisi, Ivan; D'Onofrio, Mara; Giallonardo, Anna Teresa; Piscopo, Paola; DI BONAVENTURA, Carlo. - In: NEUROLOGY. - ISSN 0028-3878. - (2023). [10.1212/WNL.0000000000207799]

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

Biagio Orlando
Co-primo
;
Alessandra Morano
Co-primo
;
Valeria Manzini
Secondo
;
Emanuele Cerulli Irelli;Enrico Michele Salamone;Chiara D'Amelio;Elisa Moliterni;Sandra Giustini;Gabriele Ruffolo;Mara D'Onofrio;Anna T Giallonardo;Carlo Di Bonaventura
Ultimo
2023

Abstract

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.
2023
tuberous sclerosis complex; biomarkers; plasma; GFAP; tau
01 Pubblicazione su rivista::01a Articolo in rivista
Plasma biomarker profile and clinical correlations in adult patients with tuberous sclerosis complex / Orlando, Biagio; Morano, Alessandra; Manzini, Valeria; CERULLI IRELLI, Emanuele; S Borioni, Maria; Veroni, Caterina; Salamone, ENRICO MICHELE; D'Amelio, Chiara; Moliterni, Elisa; Giustini, Sandra; Ruffolo, Gabriele; Arisi, Ivan; D'Onofrio, Mara; Giallonardo, Anna Teresa; Piscopo, Paola; DI BONAVENTURA, Carlo. - In: NEUROLOGY. - ISSN 0028-3878. - (2023). [10.1212/WNL.0000000000207799]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1688630
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