Leukocyte telomere shortening in Huntington's disease

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG repeat. Though symptom onset commonly occurs at midlife and inversely correlates with the CAG repeat expansion, age at clinical onset and progression rate are variable. In the present study we investigated the relationship between leukocyte telomere length (LTL) and HD development. LTL was measured by real-time PCR in manifest HD patients (HD, n = 62), pre-manifest HD patients (pre-HD, n = 38), and age-matched controls (n = 76). Significant LTL differences were observed between the three groups (p < .0001), with LTL values in the order: HD < pre-HD < controls. The relationship between LTL and age was different in the three groups. An inverse relationship between mean LTL and CAG repeat number was found in the pre-HD (p = .03). The overall data seem to indicate that after age 30 years, LT begins to shorten markedly in pre-HD patients according to CAG number and increasing age, up to the values observed in HD. This very suggestive picture allowed us to hypothesize that in pre-manifest HD, LTL could be a measure of time to clinical HD onset. The possible use of LTL as a reliable biomarker to track HD development and progression was evaluated and discussed.

Keywords: Biomarker; Huntington's disease development; Leukocyte telomere length; Neurodegenerative disease.