从临床表型到蛋白病:神经退行性痴呆的分子神经影像学。
From clinical phenotype to proteinopathy: molecular neuroimaging in neurodegenerative dementias.
机构信息
Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo, SP, Brazil.
Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Radiologia e Oncologia, Divisão e Laboratório de Medicina Nuclear (LIM 43), São Paulo, SP, Brazil.
出版信息
Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):24-35. doi: 10.1590/0004-282X-ANP-2022-S138.
Neurodegenerative dementias are characterized by the abnormal accumulation of misfolded proteins. However, its diagnostic criteria are still based on the clinical phenotype. The development of biomarkers allowed in vivo detection of pathophysiological processes. This article aims to make a non-systematic review of the use of molecular neuroimaging as a biomarker. Molecular neuroimaging is based on the use of radiotracers for image acquisition. The radiotracer most used in PET is 18F-fluorodeoxyglucose (FDG), with which it is possible to study the regional brain glucose metabolism. The pattern of regional hypometabolism provides neuroanatomical information on the neurodegenerative process, which, in turn, has a good specificity for each type of proteinopathy. FDG is very useful in the differential diagnosis of neurodegenerative dementias through the regional pattern of involvement, including dementia with Lewy bodies and the spectrum of frontotemporal dementia. More recently, radiotracers with specific ligands to some of the pathological proteins have been developed. Pittsburgh compound B (PIB) labeled with 11C and the ligands that use 18F (florbetapir, florbetaben and flutemetamol) are the most used radiotracers for the detection of insoluble β-amyloid peptide in Alzheimer's disease (AD). A first generation of ligands for tau protein has been developed, but it has some affinity for other non-tau protein aggregates. A second generation has the advantage of having a higher affinity for hyperphosphorylated tau protein, including in primary tauopathies.
神经退行性痴呆的特征是异常聚集的错误折叠蛋白。然而,其诊断标准仍然基于临床表型。生物标志物的发展允许在体内检测病理生理过程。本文旨在对分子神经影像学作为生物标志物的应用进行非系统性综述。分子神经影像学基于放射性示踪剂进行图像采集。在 PET 中最常用的示踪剂是 18F-氟脱氧葡萄糖(FDG),可以用它来研究脑内葡萄糖代谢的区域变化。区域性低代谢模式为神经退行性过程提供了神经解剖学信息,而这反过来又对每种类型的蛋白病变具有很好的特异性。FDG 通过受累区域模式在神经退行性痴呆的鉴别诊断中非常有用,包括路易体痴呆和额颞叶痴呆谱系。最近,已经开发出了一些针对特定病理蛋白的放射性示踪剂。用 11C 标记的匹兹堡化合物 B(PIB)和使用 18F 的配体(florbetapir、florbetaben 和 flutemetamol)是检测阿尔茨海默病(AD)中不溶性β-淀粉样肽最常用的放射性示踪剂。第一代 tau 蛋白配体已经开发出来,但它对其他非 tau 蛋白聚集体也有一定的亲和力。第二代配体的优点是对过度磷酸化的 tau 蛋白具有更高的亲和力,包括在原发性 tau 病中。