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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.<\/jats:p>","DOI":"10.1111\/cns.13429","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T08:27:16Z","timestamp":1593419236000},"page":"997-1009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Development of early diagnosis of Parkinson's disease: Illusion or reality?"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-1828","authenticated-orcid":false,"given":"Michael","family":"Ugrumov","sequence":"first","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations Institute of Developmental Biology RAS Moscow 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