Abstract
Huntington's disease (HD) is caused by an expanded CAG mutation and may show a heterogeneous clinical presentation. To date, although the age at onset mostly depends on the expanded CAG repeat number, no validated easy-to-test biomarkers exist either for following up patients progression rate or for exactly predicting age at onset (defined as the time when motor clinical manifestations first became noticeable). We tested the function of A 2A receptor, strongly expressed in the brain striatum and peripheral cells, in patients’ blood platelets and confirmed a maximum number of binding sites ( B max) higher than in controls (216 ± 9 versus 137 ± 7; p = 0.0001). We found a linear correlation between the receptor B max and the expanded CAG repeat number ( n = 52, r 2 = 0.19, p = 0.0011). When we selected the patients according to their clinical presentation (according to the predominating motor manifestations) and plotted the receptor B max against patients’ age at onset, we found a significant linear correlation only when considering those subjects with chorea predominant on all other motor symptoms ( n = 26, r 2 = 0.39, p = 0.0007). Because the typical chorea may depend on early dysfunction of the striatum in HD, peripheral A 2A amplification in blood platelets might reflect a central dysfunction in this part of the brain. Further studies on a larger sample size should confirm whether the analysis of A 2A-receptor binding in patients’ blood could be a useful clinical marker according to the patients’ phenotype.
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