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We read with interest the article published by Djaldetti et al. entitled “Lesions outside the CNS in Parkinson's disease”.1 As stated by the authors, understanding of the clinical features and progression of Parkinson's disease (PD) has changed significantly following the proposal by Braak et al.2 of different pathological stages in the progression of the disease in the CNS. They have clearly shown that the degenerative process in PD is much more extensive than originally described and also affects the peripheral autonomic system. Djaldetti et al. provide a detailed review of the anatomical, physiological, and clinical features of lesions in organs outside the CNS that are involved in PD and describe their relevance to the etiology, pathogenesis, and diagnosis of this disease. A section dealing with the changes observed in peripheral blood is also included in the review. In this section, the authors mention the recent evidence by Kim et al.3 of increased expression of alpha-synuclein in peripheral blood mononuclear cells (PBMC) as a potential link between the CNS and the peripheral immune system. However, we could not find any mention on a number of studies from our group and others dealing with the characterization of the changes of the dopaminergic system in PBMC from patients with PD. In particular, human PBMC synthesizes catecholamines, including dopamine, and expresses dopamine receptors and the dopamine transporter on their cell membrane. Changes of the expression of dopamine receptors in PBMC have been reported in PD,4, 5 as well as the reduction of intracellular dopamine concentration and tyrosine-hydroxylase immunoreactivity.6 In addition, a number of studies also showed the reduction of dopamine transporter immunoreactivity in PBMC from patients with PD.7–9 Although this latter phenomenon has also been observed in other neurodegenerative disorders, such as multiple system atrophy10 or amyotrophic lateral sclerosis,11 and appears, therefore, not specific for PD, we believe that these findings deserve to be mentioned as further evidence of the involvement of peripheral dopaminergic system in PD. PBMC may as well represent a useful model that can be used to further investigate the adaptation of endogenous dopaminergic systems to pharmacological interventions.

References

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  • 1
    Djaldetti R,Lev N,Melamed E. Lesions outside the CNS in Parkinson's disease. Mov Disord 2009; 24: 793800.
  • 2
    Braak H,Del Tredici K,Rub U,de Vos RA,Jansen Steur EN,Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003; 24: 197211.
  • 3
    Kim S,Seo JH,Suh YH. αlpha-synuclein, Parkinson's disease, and Alzheimer's disease. Parkinsonism Relat Disord 2004; 10: S9S13.
  • 4
    Nagai Y,Ueno S,Saeki Y,Soga F,Hirano M,Yanagihara T. Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson's disease. Neurology 1996; 46: 791795.
  • 5
    Barbanti P,Fabbrini G,Ricci A, et al. Increased expression of dopamine receptors on lymphocytes in Parkinson's disease. Mov Disord 1999; 14: 764771.
  • 6
    Caronti B,Tanda G,Colosimo C, et al. Reduced dopamine in peripheral blood lymphocytes in Parkinson's disease. Neuroreport 1999; 10: 29072910.
  • 7
    Caronti B,Antonini G,Calderaro C, et al. Dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. J Neural Transm 2001; 108: 803807.
  • 8
    Pellicano C,Buttarelli FR,Circella A, et al. Dopamine transporter immunoreactivity in peripheral blood lymphocytes discriminates Parkinson's disease from essential tremor. J Neural Transm 2007; 114: 935938.
  • 9
    Buttarelli FR,Capriotti G,Pellicano C, et al. Central and peripheral dopamine transporter reduction in Parkinson's disease. Neurol Res 2009 [Epub ahead of print].
  • 10
    Buttarelli FR,Circella A,Pellicano C, et al. Dopamine transporter immunoreactivity in peripheral blood lymphocytes in multiple system atrophy. J Neural Transm 2009; 116: 161165.
  • 11
    Buttarelli FR,Circella A,Pellicano C,Pontieri FE. Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis. Eur J Neurol 2006; 13: 416418.

Francesco E. Pontieri MD*, Carlo Colosimo MD*, * Department of Neurological Sciences, University ‘Sapienza’, Rome, Italy.