EXTRAPYAMIDAL DYSFUNCTION IN NEURODEGENERATIVE DISEASES

这个项目的目标是阐明一些药理学 患者中枢神经系统的变化 橄榄体脑桥小脑萎缩（OPCA）和阿尔茨海默病， 锥体外系征（AD/EP）。正电子发射断层扫描（PET）将在 用于检查纹状体突触前单胺能神经元的密度， [11 C]二氢丁苯那嗪和突触后D2多巴胺能神经末梢 神经递质受体与[11 C]雷氯必利。患者 锥体外系（EP）运动障碍，这些障碍的强度将 与PET研究中的发现相关。 将检验两个具体假设。(l)在OPCA患者中， 散发和显性遗传形式，纹状体密度 多巴胺能突触前末梢和含D2的神经元 多巴胺能神经递质受体将减少， 与正常对照组相比，降低的程度将 预测疾病未来演变为临床症状 多系统萎缩（MSA）。 PET将用于定量结合 纹状体单胺能突触前末梢和纹状体D2 神经递质受体在这些患者相比， 发育完全的MSA和年龄和性别相似的正常对照受试者 分布。OPCA患者疾病过程的演变 将在临床上观察，以检测那些疾病演变成 MSA，然后在开发之前获得这些病例的PET研究 的MSA将与完全发育的患者的PET研究进行比较。 MSA、未进展为MSA的OPCA患者和正常对照 所有受试者的年龄和性别分布相似。(2)阿尔茨海默 疾病（AD）中，EP运动障碍至少部分地由变性引起 多巴胺能神经递质受体的纹状体神经元 而不是来自纹状体多巴胺能突触前末梢的变性， 而锥体外系运动障碍的严重程度 与D2多巴胺能受体的减少程度相关。 宠物 将用于定量与纹状体单胺能突触前 终末和纹状体D2神经递质受体在患者 与正常人相比，伴和不伴锥体外系疾病的AD 年龄和性别分布相似的对照组。纹状体 结合研究将与EP运动的严重程度相关 通过定量临床运动检查确定的疾病。

The goal of this project is to elucidate some of the pharmacological changes in the central nervous system of patients with olivopontocerebellar atrophy (OPCA) and Alzheimer's disease with extrapyramidal signs (AD/EP). Positron emission tomography (PET) will be used to examine in the striatum the density of presynaptic monoaminergic terminals with [11C]dihydrotetrabenazine and postsynaptic D2 dopaminergic neurotransmitter receptors with [11C]raclopride. In patients with extrapyramidal (EP) motor disorders, the intensity of these disorders will be correlated with the findings in the PET studies. Two specific hypotheses will be tested. (l) In patients with OPCA, both sporadic and dominantly inherited forms, the density of striatal dopaminergic presynaptic terminals and of neurons containing D2 dopaminergic neurotransmitter receptors will be decreased in comparison with those in normal control subjects, and the degree of reduction will predict the future evolution of the disorder into clinically symptomatic multiple system atrophy (MSA). PET will be used to quantify the binding to striatal monoaminergic presynaptic terminals and to striatal D2 neurotransmitter receptors in these patients as compared to patients with fully developed MSA and normal control subjects with similar age and sex distributions. The evolution of the disease process in the OPCA patients will be observed clinically to detect those whose disorders evolve into MSA, then the PET studies of these cases obtained prior to the development of MSA will be compared with PET studies of patients with fully developed MSA, patients with OPCA who do not progress to MSA and normal control subjects, all with similar age and sex distributions. (2) In Alzheimer's disease (AD), EP motor disorders result at least in part from degeneration of striatal neurons containing D2 dopaminergic neurotransmitter receptors and not from degeneration of striatal dopaminergic presynaptic terminals, and the intensity of the extrapyramidal motor disorders is directly correlated with the degree of reduction of D2 dopaminergic receptors. PET will be used to quantify binding to striatal monoaminergic presynaptic terminals and to striatal D2 neurotransmitter receptors in patients with AD with and without extrapyramidal disorders in comparison to normal control subjects with similar age and sex distributions. The striatal binding studies will be correlated with the severity of the EP motor disorders as determined by quantitative clinical motor examinations.