Fig. 3: Stage-dependent α-synuclein proteoform enrichment in putaminal DAT, VGLUT1 and PSD95 synapses across Braak α-synuclein stages. | Nature Communications

Fig. 3: Stage-dependent α-synuclein proteoform enrichment in putaminal DAT, VGLUT1 and PSD95 synapses across Braak α-synuclein stages.

From: Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson’s disease

Fig. 3

A Syn1 α-synuclein, B pSer129 α-synuclein, and C) CTT122 α-synuclein enrichment in DAT, VGLUT1, and PSD95 synapses in the putamen across Braak α-synuclein stages (on y axis, 0 is controls) is shown. Heat maps are colour-coded for the average density of synapses positive for α-synuclein proteoforms per Braak stage (first averaged per case across all 6 ROIs, and then per Braak α-synuclein stage group), with values similar to zero in blue, high values in red, and mid values in white. Each heatmap column has its own legend, located on the right of the corresponding panel (e.g. the DAT column legend in the Syn1 panel is on the top right of the panel). Units in heatmap legends are expressed as the density of puncta positive for α-synuclein proteoforms per 100 µm³. Below each heat map column, a representative 3D surface-rendering image of DAT (magenta), VGLUT1 (red), and PSD95 (yellow) synapses positive for α-synuclein proteoforms (green) is shown (scale bar 0.5 µm). For all data points, see Supplementary Fig. 13. The Statistical test used is a two-sided LMM with age and sex as covariates, and nested for case ID. Multiple pairwise (post-hoc) and multiple testing comparison corrections were performed with the Tukey test. Exact p values: A DAT: control vs Braak 1–4 all p > 0.05, control vs Braak 5 p = 0.051, control vs Braak 6 p = 0.077; A VGLUT1 and PSD95: control vs Braak 1–6 all p > 0.05, B DAT: control vs Braak 1–2 all p > 0.05, control vs Braak 3 p = 0.007, control vs Braak 4 p = 0.036, control vs Braak 5 p = 0.006, control vs Braak 6 p = 0.121; B VGLUT1: control vs Braak 1–4 all p > 0.05, control vs Braak 5 p < 0.001, control vs Braak 6 p < 0.001; B PSD95: control vs Braak 1–3 all p > 0.05, control vs Braak 4 p = 0.098, control vs Braak 5 p < 0.001, control vs Braak 6 p < 0.001; C DAT: control vs Braak 1–3 and 5 all p > 0.05, control vs Braak 4 p = 0.061, control vs Braak 6 p = 0.012; C VGLUT1: control vs Braak 1–4 all p > 0.05, control vs Braak 5 p = 0.031, control vs Braak 6 p < 0.001; C PSD95: control vs Braak 1–3 all p > 0.05, control vs Braak 4 p = 0.061, control vs Braak 5 p = 0.004, control vs Braak 6 p < 0.001. Source data are provided as a Source Data file. α-syn α-synuclein, DAT dopaminergic transporter, PSD95 post-synaptic density 95, VGLUT1 vesicular glutamatergic transporter 1. 0.10 < p ≤ 0.05#, p < 0.05*, p < 0.01**, p < 0.001***.

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