Dopaminergic function in a family with the PARK6 form of autosomal recessive Parkinson’s syndrome Article First Online: 23 March 2005 Received: 23 November 2004 Accepted: 08 January 2005 DOI:
Cite this article as: Kessler, K., Hamscho, N., Morales, B. et al. J Neural Transm (2005) 112: 1345. doi:10.1007/s00702-005-0281-9 Summary.
A G309D mutation in the PINK1 gene in a consanguineous Spanish kindred with seven siblings, three of whom are clinically affected, has recently been shown to be a cause of the PARK6 form of autosomal-recessive Parkinson’s syndrome. In this family, we studied pre- and postsynaptic dopaminergic function using
123I-FP-CIT- and 123I-iodobenzamide-SPECT to determine binding to the presynaptic dopamine transporter (DAT) and postsynaptic D2 receptors respectively.
All three PARK6 patients showed reduced striatal DAT binding with posterior preponderance similar to sporadic idiopathic PD, but only one patient showed significant striatal asymmetry. In two of the siblings, DAT binding was markedly increased. IBZM-SPECT was normal in both patients and sibs.
Our findings indicate that
123I-FP-CIT-SPECT shows similar DAT binding in PARK6 patients compared to idiopathic Parkinson’s disease. The increased DAT binding in heterozygous PARK6 carriers may be a new very early preclinical finding, but its significance is still unclear. Keywords: Parkinson’s disease, PARK6, dopamine transporter, single photon emission tomography. References Antonini, A, Schwarz, J, Oertel, WH, Pogarell, O, Leenders, KL 1997 Long-term changes of striatal dopamine D2 receptors in patients with Parkinson’s disease: a study with positron emission tomography and [11C]raclopride. Mov Disord 12 33 38 CrossRef PubMed Google Scholar Beal, MF 2003 Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann NY Acad Sci 991 120 131 PubMed Google Scholar Benamer, HTS, Patterson, J, Grosset, DG 2000 Accurate differentiation of parkinsonian and essential tremor using visual assessment of [ 123I]-FP-CIT SPECT imaging: the [ 123I]-FP-CIT study group. Mov Disord 13 503 510 CrossRef Google Scholar Benecke, R, Strumper, P, Weiss, H 1993 Electron transfer complexes I and IV of platelets are abnormal in Parkinson’s disease but normal in Parkinson-plus syndromes. Brain 116 1451 1463 PubMed Google Scholar Bentivoglio, AR, Cortelli, P, Valente, EM, Ialongo, T, Ferraris, A, Elia, A, Montagna, P, Albanese, A 2001 Phenotypic characterisation of autosomal recessive PARK6-linked parkinsonism in three unrelated Italian families. Mov Disord 16 999 1006 CrossRef PubMed Google Scholar Bernheimer, H, Birkmayer, W, Hornykiewicz, O, Jellinger, K, Seitelberger, F 1973 Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20 415 455 CrossRef PubMed Google Scholar Cheon, KA, Ryu, YH, Kim, YK, Namkoong, K, Kim, CH, Lee, JD 2003 Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity disorder. Eur J Nucl Med Mol Imaging 30 306 311 PubMed Google Scholar Cheon, KA, Ryu, YH, Namkoong, K, Kim, CH, Kim, JJ, Lee, JD 2004 Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette’s disorder. Psychiatry Res 130 85 95 PubMed Google Scholar
Fahn S, Elton RL (1987) Unified Parkinson’s Disease rating scale. In: Fahn S et al. (eds) Recent development in Parkinson’s disease II. McMillan Healthcare Information, Florham Park (NJ), pp 153–163
Foley, P, Riederer, P 2000 Influence of neurotoxins and oxidative stress on the onset and progression of Parkinon’s disease. J Neurol 247 82 94 Google Scholar Gainetdinov, RR, Caron, MG 2003 Monoamine transporters: from genes to behavior. Ann Rev Pharmacol Toxicol 43 261 284 CrossRef Google Scholar Hilker, R, Klein, C, Ghaemi, M, Kis, B, Strotmann, T, Ozelius, LJ, Lenz, O, Vieregge, P, Herholz, K, Heiss, WD, Pramstaller, PP 2001 Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene. Ann Neurol 49 367 376 CrossRef PubMed Google Scholar Jenner, P, Olanow, CW 1996 Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47 161 170 Google Scholar Kaasinen, V, Ruottinen, HM, Nagren, K, Lehikoinen, P, Oikonen, V, Rinne, JO 2000 Upregulation of putaminal dopamine D2 receptors in early Parkinson’s disease: a comparative PET study with [11C] raclopride and [11C]N-methylspiperone. J Nucl Med 41 65 70 PubMed Google Scholar Khan, NL, Valente, EM, Bentivoglio, AR, Wood, NW, Albanese, A, Brooks, DJ, Piccini, P 2002 Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an 18F-dopa PET study. Ann Neurol 52 849 853 CrossRef PubMed Google Scholar Lavalaye, J, Booij, J, Reneman, L, Habraken, JBA, van Royen, EA 2000 Effect of age and gender on dopamine transporter imaging with 123I-FP-CIT SPET in healthy volunteers. Eur J Nucl Med Mol Imaging 27 867 869 CrossRef Google Scholar Oliveira, SA, Scott, WK, Martin, ER, Nance, MA, Watts, RL, Hubble, JP, Koller, WC, Pahwa, R, Stern, MB, Hiner, BC, Ondo, WG, Allen, FHJ, Scott, BL, Goetz, CG, Small, GW, Mastaglia, F, Stajich, JM, Zhang, F, Booze, MW, Winn, MP, Middleton, LT, Haines, JL, Pericak-Vance, MA, Vance, JM 2003 Parkin mutations and susceptibility alleles in late-onset Parkinson’s disease. Ann Neurol 53 624 629 CrossRef PubMed Google Scholar Piccini, P, Morrish, PK, Turjanski, N, Sawle, GV, Burn, DJ, Weeks, RA, Mark, MH, Maraganore, D, Lees, AJ, Brooks, DJ 1997 Dopaminergic functions in familial Parkinson’s disease: a clinical and 18F-DOPA positron emission tomography study. Ann Neurol 41 222 229 CrossRef PubMed Google Scholar
Plotkin M, Amthauer H, Klaffke S, Kühn A, Lüdemann L, Arnold G, Wernecke K-D, Kupsch A, Felix R, Venz S (2004) Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm (DOI 10.1007/200702-004-0208-x; epub ahead of print)
Samii, A, Markopoulou, K, Wszolek, ZK, Sossi, V, Dobko, T, Mak, E, Calne, DB, Stoessl, AJ 1999 PET studies of parkinsonism associated with mutation in the alpha-synuclein gene. Neurology 53 2097 2102 PubMed Google Scholar Schwarz, J, Tatsch, K, Arnold, G, Ott, M, Trenkwalder, C, Kirsch, CM, Oertel, WH 1993 123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism. Neurology 43 S17 S20 PubMed Google Scholar Sidhu, A, Wersinger, C, Vernier, P 2004 Alpha-synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson’s disease. FEBS Lett 565 1 5 CrossRef PubMed Google Scholar Sjoholm, H, Bratlid, T, Sundsfjord, J 2004 123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia. Psychopharmacology (Berl) 173 27 31 CrossRef Google Scholar Valente, EM, Bentivoglio, AR, Dixon, PH, Ferraris, A, Ialongo, T, Frontali, M, Albanese, A, Wood, NW 2001 Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35–p36. Am J Hum Genet 68 895 900 CrossRef PubMed Google Scholar Valente, EM, Abou-Sleiman, PM, Caputo, V, Muqit, MMK, Harvey, K, Gispert, S, Ali, Z, Del Turco, D, Bentivoglio, AR, Healy, DG, Albanese, A, Nussbaum, R, Gonzalez-Maldonado, R, Deller, T, Salvi, S, Cortelli, P, Gilks, WP, Latchman, DS, Harvey, RJ, Dallapiccola, B, Auburger, G, Wood, NW 2004 Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304 1158 1160 CrossRef PubMed Google Scholar Valente, EM, Brancati, F, Ferraris, A, Graham, EA, Davis, MB, Breteler, MM, Gasser, T, Bonifati, V, Bentivoglio, AR, De Michele, G, Durr, A, Cortelli, P, Wassilowsky, D, Harhangi, BS, Rawal, N, Caputo, V, Filla, A, Meco, G, Oostra, BA, Brice, A, Albanese, A, Dallapiccola, B, Wood, NW 2002 PARK6-linked parkinsonism occurs in several European families. Ann Neurol 51 14 18 CrossRef PubMed Google Scholar Copyright information
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