Figure 1.

Summary of the pathogenic mechanisms of SSAO/VAP-1 in exacerbating the progress of cerebral amyloid angiopathy (CAA)-AD. Through the generation of toxic metabolites from SSAO activity (ammonia, methylgioxal, formaldehyde, and H₂O₂), SSAO/VAP-1 induces the vascular degeneration on both endothelial and smooth muscle cells through several mechanisms: (i) oxidative stress, (ii) induction of apoptosis through the mitochondrial pathway, (iii) induction of the expression of pro-inflammatory molecules (selectins, VCAM, ICAM…), (iv) induction of protein and lipid crosslinking, and (v) increase in Aβ aggregation. The resulting vascular degeneration, together with the protein and lipid crosslinkage and the Aβ aggregation contribute to the vascular degeneration and the CAA pathology, and these generate a positive feedback loop reinforcing SSAO/VAP-1 overexpression. Aβ aggregation itself also contributes to the SSAO/VAP-1 increase.