Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene
Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene
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DOI：
10.1002/ana.74
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发表时间：
2001-03-01
影响因子：
11.2
通讯作者：
Pramstaller, PP
中科院分区：
文献类型：
--
作者：
Hilker, R;Klein, C;Pramstaller, PP
最近描述了来自南蒂罗尔（意大利北部）的一个亲属，患有家族性、成人发病的帕金森病，属于假显性遗传，并且帕金基因发生突变。为了深入了解这种遗传性帕金森病的基底神经节功能障碍，我们对 5 名受影响的家庭成员和 5 名已证实存在复合杂合或杂合帕金突变的无症状亲属进行了 18-氟多巴 (FDOPA) 和 C-11-雷氯必利 (RAC) 正电子发射断层扫描 (PET)。将结果与健康对照受试者和典型散发性特发性帕金森病患者的结果进行比较。与散发性帕金森病组的研究结果类似，复合杂合性帕金突变患者的突触前纹状体 FDOPA 储存量减少，其中壳核后部的减少最为显着。随着突触前 FDOPA 摄取的降低，我们发现与携带杂合性 Parkin 突变、散发性帕金森病和对照受试者的无症状家庭成员相比，所有受影响的家庭成员的纹状体 C-11-雷氯必利结合指数均匀降低。我们的 PET 数据提供的证据表明，该家族的帕金森病与突触前多巴胺能功能障碍（类似于特发性帕金森病病理生理学）以及突触后 D2 受体水平的改变有关。在具有明显正常等位基因的单一 Parkin 突变的无症状携带者中，我们发现与所有纹状体区域的对照受试者相比，平均 FDOPA 摄取量有轻微但具有统计学意义的下降。这些数据表明这些受试者的临床前疾病过程。
A kindred from South Tyrol (northern Italy) with familial, adult-onset parkinsonism of pseudo-dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and C-11-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson's disease. Similar to findings in the sporadic Parkinson's disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal C-11-raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects.