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

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.

Leukocyte Telomere Length as Potential Biomarker of HD Progression: A Follow-Up Study

“…In the present study, we confirmed this result and found that the LTL in pre-HD patients has intermediate values between the controls and the manifest HD patients, being far shorter than in the controls and significantly longer than in the manifest HD patients over a follow-up interval of just 3 years. The LTL in the manifest HD patients (median 0.66 T/S) was markedly shortened compared to the other neurodegenerative diseases we studied to date: Alzheimer’s disease (mean LTL 0.70 T/S) [ 24 ], spinocerebellar ataxia 1 (SCA1) (median LTL 0.75 T/S), SCA2 (median LTL 1.06 T/S), and SCA3 (median LTL 0.90 T/S) [ 27 ]. There is ample evidence that leukocyte telomere shortening is a common hallmark of conditions associated with increased systemic oxidative stress and chronic inflammation [ 14 ].…”

“…Shortened leukocyte telomere length (LTL) has been found to be associated with various diseases, including cardiovascular diseases [ 17 ], diabetes and metabolic syndrome [ 18 , 19 ], psychological disorders [ 20 ], and autoimmune diseases [ 21 ]. Reduced LTL can also be observed in neurodegenerative diseases such as Alzheimer’s disease (AD) [ 22 , 23 , 24 , 25 ], HD [ 26 ], and some forms of spinocerebellar ataxias (SCA) [ 27 ], whereas no consistent evidence of shorter telomere length in Parkinson disease (PD) has been found [ 28 ].…”

Maternal stress-induced changes in adolescent and adult offspring: Neurobehavioural improvement and telomere maintenance

“…superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GRx) are naturally activated in the system and protect the cellular physiology [ 9 , 10 ]. The stress defence mechanism is inherent in the developing brain to protect against cellular damage [ 11 ], changes in defence mechanism/elevation of reactive oxygen species (ROS) can contribute to neuronal damage, alter neurobehavioural changes, and induces genomic instability associated with telomere length [ [12] , [13] , [14] ]. Telomere length and associated regulatory molecules have been recognized as biological markers for cellular aging and psychological stress.…”