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
Affiliations
Daniela Scarabino
Institute of Molecular Biology and Pathology, National Research Council, 00185 Rome, Italy
Liana Veneziano
Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy
Alessia Fiore
Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy
Suran Nethisinghe
Ataxia Center, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College, London WC1N 3BG, UK
Elide Mantuano
Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy
Hector Garcia-Moreno
Ataxia Center, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College, London WC1N 3BG, UK
Gianmarco Bellucci
Department of Neurosciences, Mental Health and Sensory Organs, Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, 00185 Rome, Italy
Nita Solanky
Ataxia Center, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College, London WC1N 3BG, UK
Maria Morello
Department of Experimental Medicine and Surgery, Tor Vergata University, 00133 Rome, Italy
Ginevra Zanni
Unit of Neuromuscolar and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Research Hospital, IRCCS, 00100 Rome, Italy
Rosa Maria Corbo
Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy
Paola Giunti
Ataxia Center, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College, London WC1N 3BG, UK
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.
