Fig. 1
Study workflow and characterization of microvessel preparations used for the proteomic analysis. a Study workflow (top): Parenchymal microvessels were isolated from cryopreserved post-mortem brain samples of patients with cerebral amyloid angiopathy type 1 (CAA), control subjects (CON) or patients with Alzheimer’s disease (AD) and analyzed by LC–MS/MS. Confocal microscopy images (bottom) of a brain tissue section of a representative CAA, control and AD case immunostained for the amyloid beta (Aβ) peptide (red) and for the basement membrane marker collagen IV (pseudocoloured in white). Prominent vascular Aβ immunoreactivity in arterioles and capillaries (indicated by filled yellow arrows) are only observed in CAA. Parenchymal amyloid plaques, indicated by empty yellow arrows, are observed in CAA and AD. b Confocal microscopy image of a capillary network isolated from a CAA patient with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) and stained for Aβ (red) and for the basement membrane marker collagen IV (pseudocoloured in white). c, d Level of the amyloid species Aβ1-40 (c) and Aβ1-42 (d) in the microvessel extracts determined by ELISA. p-values were calculated using ANOVA with Tukey post hoc analysis, **p = 0.0078, ****p < 0.0001. Of note, the HCHWA-D case showed the highest levels of both Aβ1-40 (40,929 pg/μg) and Aβ1-42 (1699 pg/μg) across all samples