A voxel-based PET study of dopamine transporters in Parkinson's disease: Relevance of age at onset

被引:21
作者
Panzacchi, Andrea [2 ]
Moresco, Rosa Maria [1 ,3 ]
Garibotto, Valentina [1 ]
Antonini, Angelo
Gobbo, Clara [2 ]
Isaias, Ioannis U. [4 ]
Goldwurm, Stefano
Bonaldi, Lorena [3 ]
Carpinelli, Assunta [3 ]
Pezzoli, Gianni [4 ]
Fazio, Ferruccio [1 ,2 ,3 ]
Perani, Daniela [2 ]
机构
[1] Univ Milano Bicocca, Milan, Italy
[2] Ist Sci San Raffaele, Dept Nucl Med, I-20132 Milan, Italy
[3] CNR, IBFM, I-20133 Milan, Italy
[4] Ist Clin Perfezionamento, Dept Neurosci, Parkinson Ctr, Milan, Italy
关键词
dopamine transporter; C-11]FECIT PET; Parkinson's disease; age at onset; genetics;
D O I
10.1016/j.nbd.2008.03.012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We used positron emission tomography (PET) and the dopamine transporter (DAT) ligand [C-11]FECIT to measure loss of nigrostriatal dopaminergic neurons in early phase of early onset (EOPD) and late onset Parkinson's disease (LOPD). The analysis was carried out with both regions of interest and voxelwise method (SPM2), at group and single subject levels. Genetic analysis tested for the mutations occurring most frequently in Caucasian population. A significant, bilateral, asymmetric DAT reduction was observed in both EOPD and LCPD. Noteworthy, the side and severity of DAT binding reduction significantly correlated with the severity and asymmetry of motor clinical scores. The two EOPD patients carrying mutations in the PARK2 and PARK6 genes, respectively, displayed the lowest values, bilaterally. This work demonstrates that severity of nigrostriatal damage in early disease phase of sporadic PD is not dependent on age at onset. Genetically determined PD is associated with more severe and widespread dopaminergic impairment. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:102 / 109
页数:8
相关论文
共 43 条
[1]   Striatal dopaminergic denervation in early and late onset Parkinson's disease assessed by PET and the tracer [11C]FECIT:: preliminary findings in one patient with autosomal recessive parkinsonism (Park2) [J].
Antonini, A ;
Moresco, RM ;
Gobbo, C ;
De Notaris, R ;
Panzacchi, A ;
Barone, P ;
Bonifati, V ;
Pezzoli, G ;
Fazio, F .
NEUROLOGICAL SCIENCES, 2002, 23 (Suppl 2) :S51-S52
[2]   Novel parkin mutations detected in patients with early-onset Parkinson's disease [J].
Bertoli-Avella, AM ;
Giroud-Benitez, JL ;
Akyol, A ;
Barbosa, E ;
Schaap, O ;
van der Linde, HC ;
Martignoni, E ;
Lopiano, L ;
Lamberti, P ;
Fincati, E ;
Antonini, A ;
Stocchi, F ;
Montagna, P ;
Squitieri, F ;
Marini, P ;
Abbruzzese, G ;
Fabbrini, G ;
Marconi, M ;
Libera, AD ;
Trianni, G ;
Guidi, M ;
De Gaetano, A ;
Maegawa, GB ;
De Leo, A ;
Gallai, V ;
de Rosa, G ;
Vanacore, N ;
Meco, G ;
van Duijn, CM ;
Oostra, BA ;
Heutink, P ;
Bonifati, V .
MOVEMENT DISORDERS, 2005, 20 (04) :424-431
[3]   Early-onset parkinsonism associated with PINK1 mutations -: Frequency, genotypes, and phenotypes [J].
Bonifati, V ;
Rohé, CF ;
Breedveld, GJ ;
Fabrizio, E ;
De Mari, M ;
Tassorelli, C ;
Tavella, A ;
Marconi, R ;
Nicholl, DJ ;
Chien, HF ;
Fincati, E ;
Abbruzzese, G ;
Marini, P ;
De Gaetano, A ;
Horstink, MW ;
Maat-Kievit, JA ;
Sampaio, C ;
Antonini, A ;
Stocchi, F ;
Montagna, P ;
Toni, V ;
Guidi, M ;
Dalla Libera, A ;
Tinazzi, M ;
De Pandis, F ;
Fabbrini, G ;
Goldwurm, S ;
de Klein, A ;
Barbosa, E ;
Lopiano, L ;
Martignoni, E ;
Lamberti, P ;
Vanacore, N ;
Meco, G ;
Oostra, BA .
NEUROLOGY, 2005, 65 (01) :87-95
[4]   [I-123]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease [J].
Booij, J ;
Tissingh, G ;
Boer, GJ ;
Speelman, JD ;
Stoof, JC ;
Janssen, AGM ;
Wolters, EC ;
vanRoyen, EA .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1997, 62 (02) :133-140
[5]   The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease [J].
Colloby, SJ ;
O'Brien, JT ;
Fenwick, JD ;
Firbank, MJ ;
Burn, DJ ;
McKeith, IG ;
Williams, ED .
NEUROIMAGE, 2004, 23 (03) :956-966
[6]  
de la Fuente-Fernández R, 2001, ANN NEUROL, V49, P298
[7]   Age and severity of nigrostriatal damage at onset of Parkinson's disease [J].
de la Fuente-Fernández, R ;
Lim, AS ;
Sossi, V ;
Adam, MJ ;
Ruth, TJ ;
Calne, DB ;
Stoessl, AJ ;
Lee, CS .
SYNAPSE, 2003, 47 (02) :152-158
[8]   The mystery of motor asymmetry in Parkinson's disease [J].
Djaldetti, Ruth ;
Ziv, Ilan ;
Melamed, Eldad .
LANCET NEUROLOGY, 2006, 5 (09) :796-802
[9]   A PET study of [11C]β-CIT-FE binding to the dopamine transporter in the monkey and human brain [J].
Farde, L ;
Ginovart, N ;
Halldin, C ;
Chou, YH ;
Olsson, H ;
Swahn, CG .
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2000, 3 (03) :203-214
[10]   Comparison of kindreds with parkinsonism and α-synuclein genomic multiplications [J].
Farrer, M ;
Kachergus, J ;
Forno, L ;
Lincoln, S ;
Wang, DS ;
Hulihan, M ;
Maraganore, D ;
Gwinn-Hardy, K ;
Wszolek, Z ;
Dickson, D ;
Langston, JW .
ANNALS OF NEUROLOGY, 2004, 55 (02) :174-179