Table 1.
Clinical and pathological characteristics and mean neuromelanin-containing cell density of donors included in the study.
Fig 1.
Unbiased hierarchical clustering of all gene expression profiles of iLBD, PD and control donors.
Red is control, blue is iLBD and green is PD donor. The two main clusters are formed by 1) controls and iLBD and 2) PD and iLBD, indicating that the expression of iLBD is intermediate between control and PD. Seven samples clustered separately from the two main clusters. There were no technical reasons however, to exclude these donors from the analysis.
Fig 2.
Alterations in elements of mTOR, EIF2 and EIF4 signaling pathways in Braak alpha-synuclein 1 and 2 compared to controls.
Image generated using Ingenuity pathway analysis (IPA).
Table 2.
Alterations in expression levels of alpha-synuclein and known interactors of alpha-synuclein in Braak 1–2 and PD compared to controls.
Table 3.
Alterations in expression levels of genes involved in endocytosis in the early Braak alpha-synuclein stages 1 and 2 and PD, compared to controls
Table 4.
Molecular pathways associated with the up- or down-regulated genes in end-stage PD (Braak 5–6) versus controls in our study, compared to other transcriptome studies.
Fig 3.
Schematic overview of molecular processes altered during disease progression in the SN of PD, identified using transcriptome analysis.
In Braak alpha-synuclein 1 and 2, minimal cell loss is observed along with decreased endocytosis and anterograde trafficking, and increased immune response and microglial activation. In addition, we observed down regulation of mRNA levels of the upstream regulators in mTOR pathway. In Braak alpha-synuclein 3 and 4, a steep decline in cell loss and increase in alpha-synuclein pathology is observed together disturbed regulation of protein production and apoptosis of the nigral dopaminergic cells. In Braak alpha-synuclein 5 and 6 compared to controls, severe cell loss and alpha-synuclein aggregation is observed [41]. At this advanced stage, alterations in pathways related to dopaminergic signaling and immune response are still observed.