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. 2023 Mar 1;14(3):176. doi: 10.1038/s41419-023-05672-9

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — In the healthy presymptomatic stage, the number of dopaminergic cells of SNpc slowly decreases (light blue curve), and clinical symptoms are absent. In prodromal PD, neurodegeneration starts with a rapid decrease in nigral neurons survival rate (light blue), non-motor symptoms, and signs of neurodegeneration are evident; peripheral inflammatory markers begin to increase (red dashed line). Subsequently, there is an increase in inflammatory markers, which decreases gradually in the early motor stage (red dashed line). The oligo α-syn/total α-syn ratio (gray dotted line) is elevated in both prodromal and early motor stages. In addition, the evolution of the motor impairment is represented by a green curve, especially during the late motor stage, when long-term complications of dopaminergic therapy emerge (motor fluctuations and dyskinesia). The dotted lines represent a hypothetical estimation. The duration of the healthy stage is unknown, while the prodromal stage can range between 10 and 15 years.