Fig. 5: Migrasomes derived from Aβ40 stimulated macrophages facilitate complement dependent cytotoxicity to brain blood vessels.

a BMDM derived migrasomes were collected and subjected to ITRAQ. N = 3 in both groups. Left: Diagram indicating the experimental work flow. Middle: Upregulated proteins in Aβ40-M compared with PBS-M were projected to GO-BP analysis. The top 10 GO terms were listed. Right: Volcano plot showing the deferentially expressed proteins in Aβ40-M compared with PBS-M. Gene names of proteins enriched in the GO term Complement activation were emphasized. b C5b-9 concentration in HCs (N = 12), CAA patients (N = 12), aCSVD patients (N = 9) and CADASIL patients (N = 10) (left), CAA mice models (N = 5 in Tg-SwDI/B^+/+ mice and N = 5 in 5xFAD mice) and WT (N = 5 representively in independent experiments when compared to Tg-SwDI/B^+/+ and 5xFAD mice) (middle), as well as migrasome recipients (N = 6 in each group, right). Data are presented as mean values ± SEM with the indicated significance (by one-way ANOVA followed by Tukey’s post-test or two-tailed Student’s t test). c Differential efficacy for CAA (TRUE) from HC (FALSE, diagnosis) or from patients with aCSVD or CADASIL (FALSE, differential diagnosis) was estimated with ROC analysis. N = 12 in CAA groups. N = 12 in HC group. N = 9 in aCSVD group. N = 10 in CADASIL group. d, e CAA models (Tg-SwDI/B^+/+ mice) and WT C57/BL6 mice were sacrificed at 24w of age. Coronal brain sections were collected and subjected to immunostaining. d C5b-9 deposition in brain parenchyma. e Immunostaining of CD31 (red), TSPAN4 (green) and C5b-9 (blue). Data shown are representative of 4 biologically independent experiments. Source data are provided as a Source Data file.