Cerebral amyloid angiopathy associated with hemorrhage: immunohistochemical study of 41 biopsy cases.

Abstract

The relationship between cerebral amyloid angiopathy and hemorrhage was investigated by an immunohistochemical study of biopsy cases to characterize the involvement of amyloid beta-protein, apolipoprotein E, and cystatin C in cerebral amyloid angiopathy associated with hemorrhage. The amyloid-laden vessels were examined in biopsy specimens from 41 surgical cases of sporadic cerebral amyloid angiopathy (36 cases with hemorrhage and 5 cases without hemorrhage), using immunohistochemical staining with antibodies against amyloid beta-protein, apolipoprotein E, cystatin C, and alpha-smooth muscle actin. The relationship between the occurrence, recurrence, and enlargement of the hemorrhage, and the semiquantitative estimation of the cerebrovascular amyloid-related protein deposition was analyzed using Fisher's exact test. Severe amyloid beta-protein (p < 0.013) and apolipoprotein E (p < 0.013) immunoreactivity were risk factors for the occurrence of the hemorrhage. Severe cystatin C immunoreactivity was a risk factor for the occurrence (p < 0.002) and enlargement (p < 0.014) of the hemorrhage, and tended to induce recurrent hemorrhage (p < 0.103). In addition, loss of the vascular smooth muscle was observed in the intensely amyloid-laden vascular walls that showed cystatin C-immunoreactivity. The present study indicates that intense amyloid beta-protein deposition with cystatin C deposition weakens the cerebrovascular walls, and that cystatin C deposition is a strong predictor of hemorrhage in cerebral amyloid angiopathy.