Ultrastructural evidence of early non-fibrillar Abeta42 in the capillary basement membrane of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type.

[hereditary cerebral hemorrhage with amyloidosis]

The C-terminal profile and ultrastructure of small and presumably early capillary amyloid beta protein (Abeta ) deposits were investigated in four patients with hereditary cerebral hemorrhage with amyloidosis , Dutch type . The C terminus of the 40 (Abeta 40 ) or the 42 (Abeta 42 ) amino acid form of Abeta was gold labeled in serial , ultrathin sections on glass slides for reflection contrast microscopy and on grids for electron microscopy . In all studied subjects , reflection contrast microscopy revealed capillaries with focal Abeta 42 immunolabeling in the absence of Abeta 40 labeling . In the adjacent electron microscopic section , Abeta 42 labeling was confined to the capillary basement membrane . The majority of Abeta 42 (+)40 (-) deposits showed no amyloid fibrils . Abeta 42 (+)40 (-) deposits were sometimes observed in an unremarkable basement membrane but usually showed increased electron density and reticular structures . A small subset of Abeta 42 (+)40 (-) deposits with basement membrane changes showed few amyloid fibrils . Abeta 42 (+)40 (+) capillary deposits always showed definite fibrils and were larger than Abeta 42 (+)40 (-) capillary deposits . The present findings suggest that in capillaries the accumulation and subsequent polymerization of Abeta 42 , possibly in conjunction with basement membrane changes , precedes the definite fibril formation with Abeta 40 .