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.

中文翻译：

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帕金森病早期诊断的发展：幻想还是现实？

对抗神经退行性疾病、阿尔茨海默病和帕金森病 (PD)，是 21 世纪的挑战。治疗患者的低疗效是由于在大多数特定神经元退化和神经可塑性耗尽之后，诊断和治疗开始较晚。人们认为，早期诊断（ED）和预防性治疗的发展将延缓特定症状的出现。本综述评估了开发 PD 的 ED 的方法。由于 PD 是一种全身性疾病，并且某些神经元的退化先于控制运动功能的黑质纹状体多巴胺能神经元的退化，因此目前的方法是基于搜索生物标志物，例如患者的运动前症状和体液 (BF) 的变化。然而，所有开发 ED 的尝试都没有成功。所以，建议通过 (i) 在临床阶段患者 BF 中发现的生物标志物中选择具有临床前阶段动物模型特征的生物标志物，(ii) 搜索前驱期受试者 BF 中的生物标志物，从而增强当前的方法，通过检测运动前症状和黑质纹状体多巴胺能系统的故障来选择。此外，提出了一种使用激发试验开发 PD ED 的新方法，该方法已成功用于内科。通过检测运动前症状和黑质纹状体多巴胺能系统的故障来选择。此外，提出了一种使用激发试验开发 PD ED 的新方法，该方法已成功用于内科。通过检测运动前症状和黑质纹状体多巴胺能系统的故障来选择。此外，提出了一种使用激发试验开发 PD ED 的新方法，该方法已成功用于内科。