Leukocyte Telomere Length Variability as a Potential Biomarker in Patients with PolyQ Diseases

Daniela Scarabino; Liana Veneziano; Alessia Fiore; Suran Nethisinghe; Elide Mantuano; Hector Garcia-Moreno; Gianmarco Bellucci; Nita Solanky; Maria Morello; Ginevra Zanni; Rosa Maria Corbo; Paola Giunti

doi:10.3390/antiox11081436

Leukocyte Telomere Length Variability as a Potential Biomarker in Patients with PolyQ Diseases

Antioxidants (Basel). 2022 Jul 24;11(8):1436. doi: 10.3390/antiox11081436.

Authors

Affiliations

¹ Institute of Molecular Biology and Pathology, National Research Council, 00185 Rome, Italy.
² Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy.
³ Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy.
⁴ Ataxia Center, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College, London WC1N 3BG, UK.
⁵ Department of Neurosciences, Mental Health and Sensory Organs, Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, 00185 Rome, Italy.
⁶ Department of Experimental Medicine and Surgery, Tor Vergata University, 00133 Rome, Italy.
⁷ Unit of Neuromuscolar and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, 00100 Rome, Italy.

Abstract

SCA1, SCA2, and SCA3 are the most common forms of SCAs among the polyglutamine disorders, which include Huntington's Disease (HD). We investigated the relationship between leukocyte telomere length (LTL) and the phenotype of SCA1, SCA2, and SCA3, comparing them with HD. The results showed that LTL was significantly reduced in SCA1 and SCA3 patients, while LTL was significantly longer in SCA2 patients. A significant negative relationship between LTL and age was observed in SCA1 but not in SCA2 subjects. LTL of SCA3 patients depend on both patient's age and disease duration. The number of CAG repeats did not affect LTL in the three SCAs. Since LTL is considered an indirect marker of an inflammatory response and oxidative damage, our data suggest that in SCA1 inflammation is present already at an early stage of disease similar to in HD, while in SCA3 inflammation and impaired antioxidative processes are associated with disease progression. Interestingly, in SCA2, contrary to SCA1 and SCA3, the length of leukocyte telomeres does not reduce with age. We have observed that SCAs and HD show a differing behavior in LTL for each subtype, which could constitute relevant biomarkers if confirmed in larger cohorts and longitudinal studies.

Keywords: biomarkers; leukocyte telomere length; neurodegenerative diseases; spinocerebellar ataxias.

Grants and funding

P.G. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre UCLH. P.G. also receives support from the North Thames CRN. P.G. and H.G.-M. work at University College London Hospitals/University College London, which receives a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centre’s funding scheme. P.G. received funding from CureSCA3 in support of H.G.-M.’s work. P.G. received funding from MRC MR/N028767/1 ESMI, and H.G.-M. is supported by the same grant as well as the FATHERS Foundation. P.G. is supported by NIHR, BRC UCLH, and CNR NORTH THAMES. R.M.C. is supported by Sapienza University of Rome (2018/2019 grants). L.V. is supported by EHDN seed fund grant 0942. L.V. is also supported by AICH (Rome, Italy).