CST1 and Alzheimer disease: In physiological conditions, CST3 is found as a monomer, but under crystallization conditions CST3 forms domain-swapped dimers.37, 38 The L68Q variant of CST3 spontaneously forms dimeric structures via domain swapping, leading to amyloid deposits in the cerebral vasculature, such as those found in hereditary cystatin C amyloid angiopathy or Alzheimer's disease.39, 40 In our study of colon and gastric cancers, a CST3 mutation was not found, but a silent mutation at Arg-91 (R91R) in CST1 was identified in both cancers (Figure 1b), although its relevance is not yet understood.