SHORT COMMUNICATION Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis F. R. Buttarelli a , A. Circella a,b , C. Pellicano a and F. E. Pontieri a a Dipartimento di Scienze Neurologiche, II Facolta ` di Medicina e Chirurgia, Universita ` degli Studi di Roma ÔLa SapienzaÕ, Viale dell’Universita `, Roma, Italy; and b Dipartimento di Scienze Biochimiche ÔA. Rossi FanelliÕ, II Facolta ` di Medicina e Chirurgia, Universita ` degli Studi di Roma ÔLa SapienzaÕ, Piazzale Aldo Moro, Roma, Italy Keywords: amyotrophic lateral sclerosis, dopamine transporter, immunocyto- chemistry, peripheral blood mononuclear cells Received 21 December 2004 Accepted 6 April 2005 Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations, and increased reflexes, with conserved intellect and higher functions. The neuropathology of ALS is mostly confined to damage of the motor neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior horns of the spinal cord. However, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the dopamine neurons has been shown by neurochemical and imaging studies in the brain and spinal cord of ALS patients. Recent reports suggest that peripheral blood mononuclear cells (PBMC) may represent a useful in vivo model to study neurochemical alterations that occur in neurodegenerative disorders. Here we demonstrate the significant reduction of dopamine transporter immunoreactivity in PBMC of patients affected by ALS with respect to healthy subjects. These results extend our knowledge of damage of the dopamine system in ALS to peripheral cells. Thus, the original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease with involvement of other neuronal systems in the central as well as peripheral nervous system. Introduction Amyotrophic lateral sclerosis (ALS) is a chronic pro- gressive neuromuscular disorder of unknown etiology, characterized by loss of the motor neurons in the cer- ebral cortex, some motor nuclei of the brainstem and anterior horns of the spinal cords [1]. Symptoms include muscle wasting and fasciculations, together with spas- ticity and increased reflexes [2]. Respiratory failure is the most frequent cause of death [2]. Although the neuropathology of ALS is mostly confined to motor neurons, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the central dopamine (DA) sys- tems has been shown in ALS patients using neuro- chemical, immunohistochemical and imaging techniques [3–6], as well as in the transgenic mouse model of the disease [7]. Recent studies suggest that peripheral blood mono- nuclear cells (PBMC) may represent a useful tool with which to investigate changes in neurotransmitter- receptor system occurring in the brain in neurodegen- erative diseases. In this respect, our laboratory has shown the reduction of tyrosine-hydroxylase and dop- amine transporter (DAT) immunoreativities in PBMC of patients suffering Parkinson’s disease [8,9], as well as dynamic changes of dopamine-b-hydroxylase immu- noreactivity in PBMC of patients affected by Alzhei- mer’s disease [10]. In this study, we investigated the changes of DAT immunoreactivity in PBMC of pa- tients affected by ALS. Materials and methods Twelve patients affected by probable or definite ALS, according to the El Escorial revised criteria of the World Federation of Neurology [11], were consecu- tively recruited at the outpatient service for Motor Neuron Disease of our Institution in the period between 1 February and 30 April 2004 (seven males, five females, mean age 61±10 years, mean disease duration 14±5 months, mean ALS-Functional Rating Scale 22±3, mean FVC 60±5%). There were six bulbar- onset and eight limb-onset cases. One familial case (f-ALS) was included. ALS patients were not under ventilatory support neither they were supplemented by Correspondence: Francesco E. Pontieri, Dipartimento di Scienze Neurologiche, II Facolta` di Medicina e Chirurgia, Universita` degli Studi di Roma ÔLa SapienzaÕ, Divisione di Neurologia, Ospedale ÔSant’AndreaÕ, Via di Grottarossa, 1035–00189 Roma, Italy (tel.: +39–06 80345525; fax: +39–06 80345272; e-mail: francesco. pontieri@ospedalesantandrea.it). 416 Ó 2006 EFNS European Journal of Neurology 2006, 13: 416–418