Nordberg Agneta
Karolinska institute, Neurotec Department, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Lancet Neurol. 2004 Sep;3(9):519-27. doi: 10.1016/S1474-4422(04)00853-1.
Alzheimer's disease (AD) is the most common form of dementia and is characterised by progressive impairment in cognitive function and behaviour. The pathological features of AD include neuritic plaques composed of amyloid-beta peptide (Abeta) fibrils, neurofibrillary tangles of hyperphosphorylated tau, and neurotransmitter deficits. Increases in the concentration of Abeta in the course of the disease with subtle effects on synaptic efficacy will lead to gradual increase in the load of amyloid plaques and progression in cognitive impairment. Direct imaging of amyloid load in patients with AD in vivo would be very useful for the early diagnosis of AD and the development and assessment of new treatment strategies. Three different strategies are being used to develop compounds suitable for in vivo imaging of amyloid deposits in human brains. Monoclonal antibodies against Abeta and peptide fragments have had limited uptake by the brain when tested in patients with AD. When putrescine-gadolinium-Abeta has been injected into transgenic mice overexpressing amyloid, labelling has been observed with MRI. The small molecular approach for amyloid imaging has so far been most successful. The binding of different derivatives of Congo red and thioflavin has been studied in human autopsy brain tissue and in transgenic mice. Two compounds, fluorine-18-labelled-FDDNP and carbon-11-labelled-PIB, both show more binding in the brains of patients with AD than in those of healthy people. Additional compounds will probably be developed that are suitable not only for PET but also for single photon emission CT (SPECT).
阿尔茨海默病（AD）是最常见的痴呆形式，其特征是认知功能和行为逐渐受损。AD的病理特征包括由β-淀粉样肽（Aβ）纤维组成的神经炎性斑块、过度磷酸化tau的神经原纤维缠结以及神经递质缺陷。疾病过程中Aβ浓度的增加对突触效能有细微影响，将导致淀粉样斑块负荷逐渐增加和认知障碍进展。对AD患者体内淀粉样蛋白负荷进行直接成像，对于AD的早期诊断以及新治疗策略的开发和评估将非常有用。目前正在采用三种不同策略来开发适用于人脑淀粉样蛋白沉积物体内成像的化合物。在AD患者中进行测试时，针对Aβ的单克隆抗体和肽片段在脑中的摄取有限。将腐胺-钆-Aβ注入过度表达淀粉样蛋白的转基因小鼠后，通过磁共振成像（MRI）观察到了标记。用于淀粉样蛋白成像的小分子方法目前最为成功。已在人类尸检脑组织和转基因小鼠中研究了刚果红和硫黄素不同衍生物的结合情况。两种化合物，即氟-18标记的FDDNP和碳-11标记的PIB，在AD患者脑中的结合均多于健康人。可能会开发出不仅适用于正电子发射断层扫描（PET），还适用于单光子发射计算机断层扫描（SPECT）的其他化合物。
