Antonini A, Leenders K L, Eidelberg D
Movement Disorders Center, Department of Neurology, North Shore University Hospital, Manhasset, NY, USA.
Ann Neurol. 1998 Feb;43(2):253-5. doi: 10.1002/ana.410430216.
We used [11C]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (CAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical and symptomatic gene carriers, we found significant correlations between CAG repeat length and the ratio of percent loss in striatal D2 receptor binding divided by age. In accord with neuropathological studies, we obtained an intercept at 35.5 CAG repeats in the symptomatic HD patients. Nonetheless, we noted that the slopes of the correlation lines differed significantly for the presymptomatic and symptomatic cohorts. These PET results support the notion that the HD disease process is a function of trinucleotide length and age, and that the development of clinical signs and symptoms is associated with CAG repeat lengths greater than 35.5. However, our analysis also suggests that striatal degeneration may proceed in a nonlinear fashion. These findings have implications for the design of neuroprotective strategies for the treatment of HD.
我们使用[11C]雷氯必利和正电子发射断层扫描（PET）来评估10名无症状和8名有症状的亨廷顿舞蹈病（HD）突变携带者的纹状体多巴胺D2受体结合、三核苷酸重复数（CAG）和受试者年龄之间的关系。在临床前和有症状的基因携带者中，我们发现CAG重复长度与纹状体D2受体结合损失百分比除以年龄的比率之间存在显著相关性。与神经病理学研究一致，我们在有症状的HD患者中获得了35.5个CAG重复的截距。尽管如此，我们注意到无症状和有症状队列的相关线斜率存在显著差异。这些PET结果支持这样的观点，即HD疾病过程是三核苷酸长度和年龄的函数，并且临床体征和症状的出现与大于35.5的CAG重复长度相关。然而，我们的分析还表明纹状体变性可能以非线性方式进行。这些发现对HD治疗的神经保护策略设计具有启示意义。
