Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology RAS, Moscow, Russia.
CNS Neurosci Ther. 2020 Oct;26(10):997-1009. doi: 10.1111/cns.13429. Epub 2020 Jun 29.
The fight against neurodegenerative diseases, Alzheimer disease and Parkinson's disease (PD), is a challenge of the 21st century. The low efficacy of treating patients is due to the late diagnosis and start of therapy, after the degeneration of most specific neurons and depletion of neuroplasticity. It is believed that the development of early diagnosis (ED) and preventive treatment will delay the onset of specific symptoms. This review evaluates methodologies for developing ED of PD. Since PD is a systemic disease, and the degeneration of certain neurons precedes that of nigrostriatal dopaminergic neurons that control motor function, the current methodology is based on searching biomarkers, such as premotor symptoms and changes in body fluids (BF) in patients. However, all attempts to develop ED were unsuccessful. Therefore, it is proposed to enhance the current methodology by (i) selecting among biomarkers found in BF in patients at the clinical stage those that are characteristics of animal models of the preclinical stage, (ii) searching biomarkers in BF in subjects at the prodromal stage, selected by detecting premotor symptoms and failure of the nigrostriatal dopaminergic system. Moreover, a new methodology was proposed for the development of ED of PD using a provocative test, which is successfully used in internal medicine.
对抗神经退行性疾病，如阿尔茨海默病和帕金森病（PD），是 21 世纪的挑战。治疗患者的效果不佳，是因为在大多数特定神经元变性和神经可塑性丧失后，才进行晚期诊断和开始治疗。人们认为，早期诊断（ED）和预防性治疗的发展将延迟特定症状的出现。本综述评估了开发 PD 的 ED 的方法学。由于 PD 是一种全身性疾病，并且某些神经元的变性先于控制运动功能的黑质纹状体多巴胺能神经元的变性，因此目前的方法学基于寻找生物标志物，如前驱症状和患者体液（BF）的变化。然而，所有开发 ED 的尝试都没有成功。因此，建议通过以下方式增强当前的方法学：（i）在临床阶段患者的 BF 中发现的生物标志物中选择那些与临床前阶段动物模型特征相符的生物标志物；（ii）在通过检测前驱症状和黑质纹状体多巴胺能系统失败而选择的前驱期受试者的 BF 中寻找生物标志物。此外，还提出了一种使用在临床医学中成功使用的激发试验开发 PD 的 ED 的新方法学。
