Fig. 5

Hypothetical molecular mechanisms in cerebral cortical vessels of CAA patients. Based on the results in the present study, we illustrate the features of pathological molecular mechanisms that occur in cerebral cortical vessels of CAA patients. Red, proteins showing either significant upregulation in ADNC +/CAA +/H donors or significant positive correlations with Aβ or COL6A2. Blue, proteins showing either significant downregulation in ADNC +/CAA +/H donors or significant negative correlations with Aβ or COL6A2. Gray, proteins which were not quantified in the present study. The proteins whose significant change in protein expression in CAA capillary was clarified for the first time in the present study were surrounded with solid line. The proteins whose change in protein expression in CAA capillary or CAA model has been already reported were surrounded with broken line. The mutual relationship of individual molecules was based on our literature search. The present study revealed that a variety of molecules in the fibrosis pathway including ECM, adhesion and TGF-β signal proteins were activated. Furthermore, the activation of oxidative stress-related molecules and the inactivation of AKT signalling molecules are also shown, and these would have activated the apoptosis pathway including caspase signal. The activation of fibrosis and apoptosis leads to the suppression of the Aβ clearance and the destruction of cerebral vessels. Based on literature search, HSP90A, CD44, and CA1 are considered as therapeutic targets of taxifolin, verbascoside, and acetazolamide, respectively. The upregulation of these three proteins in CAA capillaries were clarified for the first time in the present study. The molecular mechanisms illustrated here would be useful for better understanding of the CAA pathology and for promoting the discovery and development of drugs and biomarkers for CAA