Harvard Medical School, Massachusetts General Hospital/ Athinoula A. Martinos Center for Biomedical Imaging, Building 149, 13th Street, Room 2301, Charlestown, MA 02129, USA.
Ann Nucl Med. 2010 Feb;24(2):55-66. doi: 10.1007/s12149-009-0330-9.
The increasing life expectancy in our society results in a continuously growing number of patients suffering from neurodegenerative disorders, particularly Alzheimer's disease (AD). Apart from the deleterious consequences for patients and their relatives, this issue has also alarming effects on our social systems. These facts have justified increased scientific efforts regarding the identification of basic pathomechanisms of dementia and the development of new treatment options. Increased production of specific proteins and their pathologic aggregation in the brain appears to be a pathomechanism which occurs early in the course of many different neurodegenerative diseases. Among the most well-known of these protein aggregations are amyloid plaques, which arise from the aggregation of the β-amyloid protein. Currently, this amyloid-aggregation pathology is regarded as a key pathology, playing a causal role in the development of AD. Consequently, modern therapy approaches are directed towards this target. Limited access to brain tissue has so far restricted the definite diagnosis of AD to postmortem histopathological assessment of brain tissue. For the same reason, a clear association between extent of amyloid deposition pathology and clinical course of AD has not been established so far. However, particularly with regard to new therapeutic options, a reliable in vivo diagnosis is required. Modern molecular imaging tracers such as [11C]PIB do now open the possibility to visualize amyloid depositions in vivo, using positron emission tomography. This type of "in vivo histopathology" approach allows the characterization of neurodegenerative disorders on the basis of the underlying pathology rather than on their symptomatic appearance. In this manuscript, we will discuss the options of amyloid-plaque imaging regarding early and differential diagnosis of different forms of dementia as well as for patient selection for therapy trials and for objective therapy monitoring.
在我们的社会中，预期寿命的延长导致患有神经退行性疾病的患者数量不断增加，尤其是阿尔茨海默病（AD）。除了给患者及其亲属带来不利后果外，这一问题对我们的社会系统也产生了惊人的影响。这些事实证明，增加针对痴呆基本病理机制的识别和新治疗方法的开发的科学努力是合理的。特定蛋白质的产量增加及其在大脑中的病理性聚集似乎是许多不同神经退行性疾病早期发生的病理机制。在这些蛋白质聚集物中，最著名的是淀粉样斑块，它是由β-淀粉样蛋白聚集引起的。目前，这种淀粉样蛋白聚集病理被认为是关键的病理机制，在 AD 的发展中起因果作用。因此，现代治疗方法针对这一目标。由于脑组织的获取有限，迄今为止，AD 的明确诊断仅限于对脑组织进行死后组织病理学评估。出于同样的原因，迄今为止，尚未确定淀粉样蛋白沉积病理学与 AD 临床病程之间的明确关联。然而，特别是对于新的治疗选择，需要进行可靠的体内诊断。现代分子成像示踪剂，如[11C]PIB，现在使用正电子发射断层扫描（PET），为体内可视化淀粉样蛋白沉积提供了可能性。这种“体内组织病理学”方法允许基于潜在病理学而不是症状表现来对神经退行性疾病进行特征描述。在本文中，我们将讨论淀粉样斑块成像在不同形式痴呆的早期和鉴别诊断、治疗试验患者选择以及客观治疗监测方面的选择。
