Abstract
Background Blood biomarkers to improve the management of pre-manifest Huntington’s disease (pre-HD) are actively searched We investigated the telomere length (TL) and DNA damage signatures (DDS) in peripheral lymphocytes from pre-HD individuals and HD patients, as potential predictive biomarkers. Methods We studied 58 HD and 23 pre-HD subjects with comparable CAG repeats, and 44 age/sex-matched healthy controls (HC). Phosphorylated γ-H2AX (pγ-H2AX) fluorescence, which marks double strand DNA breaks, and the TL were studied by cytofluorimetry and qPCR. Results Peripheral lymphocytes from pre-HD and HD groups showed significant DDS than HC. The odds ratio was Conclusions Peripheral lymphocytes from pre-HD subjects display progressive DDS in absence of clinical and signs. The basal levels of DDS are predictive of disease progression over time. DDS may represent a biomarker with unprecedented features (accessible, clearly detectable in pre-manifest HD, negligible HC, potential reversible).
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