Quantification of serum TDP-43 and neurofilament light chain in patients with amyotrophic lateral sclerosis stratified by UNC13A genotype.

Autor: Casiraghi V; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy., Milone I; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy., Brusati A; Department of Brain and Behavioral Sciences, University of Pavia, Via Bassi 21, 27100 Pavia, Italy., Peverelli S; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy., Doretti A; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy., Poletti B; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy., Maderna L; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy., Morelli C; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy., Ticozzi N; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; 'Dino Ferrari' Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy., Silani V; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; 'Dino Ferrari' Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy., Verde F; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; 'Dino Ferrari' Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy., Ratti A; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy; Department of Neuroscience - Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy. Electronic address: a.ratti@auxologico.it.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2024 Nov 15; Vol. 466, pp. 123210. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1016/j.jns.2024.123210
Abstrakt: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative condition affecting upper and/or lower motor neurons and characterized neuropathologically by TDP-43 proteinopathy. Given its role in ALS pathobiology, it is currently under debate whether TDP-43 might represent a suitable ALS biomarker to be measured in patients' biofluids. The rs12608932 A > C single nucleotide polymorphism in the UNC13A gene is a risk factor for ALS and patients homozygous for the high-risk C allele display a higher burden of TDP-43 neuropathology than homozygotes for the low-risk A allele, although the association with TDP-43 levels in biofluids has never been evaluated. In this study, we measured serum levels of TDP-43 and neurofilament light chain (NFL) by Simoa technology in a cohort of 69 ALS patients stratified according to the UNC13A rs12608932 genotype compared to 43 neurologically healthy controls. By multiple linear regression analysis, serum TDP-43 was significantly elevated in ALS patients compared to controls, with UNC13A AA and AC, but not CC, ALS patients showing higher serum TDP-43 levels than controls. We also confirmed that serum NFL concentration was increased in ALS patients, without any correlation with the UNC13A genotype. Our results indicate that serum TDP-43 is higher in ALS patients compared to controls and that, in contrast to NFL, this increase is specifically associated with the UNC13A rs12608932 AA and AC genotypes, but not with the high-risk CC genotype. Studies in larger cohorts will be needed to confirm these findings and to elucidate the biological link between serum TDP-43 levels and UNC13A genotype.
Competing Interests: Declaration of competing interest FV is Associate Editor of Journal of Alzheimer's Disease. The other Authors declare that they have no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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