Neuroscience Letters 393 (2006) 27–30 The platelet maximum number of A 2A -receptor binding sites (B max ) linearly correlates with age at onset and CAG repeat expansion in Huntington’s disease patients with predominant chorea Vittorio Maglione a , Milena Cannella a , Tiziana Martino a , Antonio De Blasi b , Luigi Frati c,d , Ferdinando Squitieri a,∗ a Neurogenetics Unit, IRCCS INM Neuromed, Localit` a Camerelle, 86077 Pozzilli (IS), Italy b Cellular and Molecular Neurobiology Unit, IRCCS INM Neuromed, Pozzilli (IS), Italy c Department of Experimental Medicine and Pathology, University “La Sapienza” Rome, Italy d IRCCS Neuromed, Pozzilli (IS), Italy Received 21 July 2005; received in revised form 24 August 2005; accepted 14 September 2005 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. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Age at onset; Onset chorea; A 2A -receptor dysfunction; B max ; CAG repeat expansion; Platelets Huntington’s disease (HD) is caused by a CAG expansion muta- tion translated into an elongated poly(Q) stretch in huntingtin, a protein widely expressed in many tissues [14]. The initial motor symptoms may be heterogeneously manifested and character- ized either by chorea or, in about 8% cases, by extrapyramidal symptoms other than choreic movements [10]. Severe behav- ioral changes may sometimes precede the movement disorder by many years [12,16]. Although the age at onset mostly depends on the expanded CAG repeat number, no changes in easy-to- test biological variables can exactly predict age at onset, nor its propensity to anticipate within families [15]. An aberrant ampli- fication of adenosine A 2A -receptor signaling documented in ∗ Corresponding author. Tel.: +39 0865 915238; fax: +39 0865 927575. E-mail address: neurogen@neuromed.it (F. Squitieri). peripheral blood cells of subjects with HD nevertheless implies that this cellular dysfunction may be related to clinical and genetic features [3]. We analyzed A 2A -receptor function in blood platelets from patients selected according to their clinical presentation. Because the dysfunction of the striatum, the brain structure most involved in HD, has been proposed as the main cause of chorea in HD [7], we analyzed receptor function focusing on patients in whom clinical features of chorea predominated over all other motor symptoms. We studied A 2A receptors in platelets because platelets are easily obtained in large amounts simply by draw- ing a blood sample, have an embryological origin common to neurons [1] and may resemble central neurons [4,5]. Patients were periodically evaluated by the Unified Hunting- ton Disease Rating Scale (UHDRS) and genetic laboratory test- 0304-3940/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2005.09.037