FIGURE 7.

The increase of the mitophagy marker pS65‐Ub in human autopsy brain is associated with LB‐, but not GCI‐type of αsyn pathology. (A) The schematic shows that αsyn pathology is predominantly found in the amygdala and to a lesser extent in the nbM and putamen in LBD, while it is predominantly found in the putamen and to a lesser extent in the amygdala and nbM in MSA. (B) Representative images of αsyn (NACP, top), pS65‐Ub (middle), and phospho‐tau (CP13, bottom) immunostaining in the amygdala and putamen of LBD^mut and MSA cases, respectively. Scale bar: 25 μm. Insets show magnified views of cortical type LBs in LBD, GCIs in MSA, and pS65‐Ub positive cells. (C) Consistent with the schematic, NACP intensity is differentially increased in the amygdala, nbM, and putamen of LBD^mut and MSA cases compared to age‐matched controls (p = 0.0015 for LBD^mut, p < 0.0001 for MSA, p < 0.01 for LBD^mut vs. MSA). (D) pS65‐Ub positive cell density is increased in all three regions, but only in the LBD^mut group compared to age‐matched controls (p = 0.004, 0.0053, and 0.0005 in the amygdala, nbM, and putamen, respectively) and MSA group (p = 0.0035, 0.0003, and 0.0013 in the amygdala, nbM, and putamen, respectively). (E) CP13 positive cell density is selectively increased in the nbM of the LBD^mut group (p = 0.0097 for LBD^mut, p = 0.0062 for LBD^mut vs. MSA) and in the putamen of MSA cases (p < 0.0001) compared to age‐matched controls. n = 11–15 for controls, n = 4–5 for LBD^mut group, n = 14–15 for MSA group. Kruskal–Wallis and Mann–Whitney U tests followed by adjustment with Bonferroni correction, *p < 0.0167 (i.e., the statistical significance threshold after Bonferroni correction), **p < 0.001, ***p < 0.0001, n.s., not significant. Data is shown as median with interquartile range. GCI, glial cytoplasmic inclusion; LB, Lewy body; nbM, nucleus basalis of Meynert.