Fig. 7: FUMA analysis of significant DEGs in iPD samples.

The analytical framework indicates that the molecular signature includes a strong component of both upregulated and downregulated transcripts that are typical of cells in the putamen and basal ganglia of the brain. a, Histogram showing that several upregulated and downregulated genes in iPD blood also participate in brain and substantia nigra function (red bars indicate statistically significant associations, Bonferroni P < 0.05; https://fuma.ctglab.nl/). b, Representative immunohistochemistry images of TH-positive neurons in the substantia nigra pars compacta of patients with iPD (PD, n = 9; HC, n = 7), displaying γH2AX foci (purple). Scale bars, 100 μm, 20 μm. c,d, Quantification of the number of γH2AX foci in TH-positive neurons (c) and TH-positive neurons displaying more than five γH2AX foci (d), which demonstrate increased signs of DNA damage in iPD brains. Violin plot in c is showing the distribution of the number of foci per nucleus in TH-positive neurons. A total of 578 neurons from HCs and 314 neurons from patients with PD were analyzed (PD mean = 1.519, s.d. = 1.887; HC mean = 1.032, s.d. = 1.392; ****P < 0.0001, two-sided Mann–Whitney test). Each dot in d represents an individual. Bars represent mean ± s.e.m. (***P < 0.0007, two-sided Mann–Whitney test).