Fig. 7: Neuronal α-syn pathology exhibits higher seeding activity than glial pathology in PD.

Aggregates of α-syn and their seeding capacity were analyzed in the amygdala of PD and MSA cases using α-syn-IHC and α-syn-isSID. Representative images of neuronal inclusions detected by α-syn-isSID in PD and MSA (gray arrows) (a). Quantification of cell inclusions detected by each technique revealed that α-syn-isSID detects more neuronal pathology in PD compared to α-syn-IHC, whereas in MSA, both techniques detected similar levels of α-syn pathology. Oligodendrocytic and astrocytic α-syn pathology showed no significant differences between α-syn-IHC and α-syn-isSID in either PD or MSA cases. Quantification of total percentage area covered by α-syn pathology (representing α-syn burden) revealed that α-syn-isSID detected more α-syn pathology than α-syn-IHC in PD cases. Statistical analysis was performed using a two-way ANOVA followed by a Bonferroni post-hoc test (*p < 0.05; **p < 0.01). Bars represent the mean + standard error of the mean. The scatter plot illustrates a strong positive correlation between α-syn-IHC and α-syn-isSID signal in PD (r = 0.84; p value = 0.0003), as revealed by Spearman’s rank correlation test (b). Consecutive PD sections subjected to short α-syn-isSID incubation times displayed more prominent neuronal α-syn inclusions compared to glial inclusions at 15 minutes, although they were still detectable and increased over time. Gray arrows indicate neuronal α-syn inclusions; blue arrows indicate glial α-syn inclusions (c). Scale bar is 100 µm.