Differences Between Vascular and Plaque Core Amyloid in Alzheimer's Disease

The predominant protein of cerebrovascular and plaque core amyloid in Alzheimer's disease, Down's syndrome, hereditary hemorrhage with amyloidosis--Dutch type, sporadic cerebral amyloid angiopathy, and age-related amyloidosis is a unique polypeptide, called beta protein. The length of the plaque amyloid protein was reported to be 42-43 residues, but the complete length of the cerebral vascular amyloid is not known. To clarify this issue, amyloid fibrils from the leptomeninges of an Alzheimer's disease patient were isolated and the primary structure determined. The complete sequence of cerebrovascular beta-amyloid protein, although homologous to the plaque core amyloid protein previously reported, has 39 residues instead of 42. Amino terminal heterogeneity is present but minimal, and it is three residues shorter at the carboxy terminus. These differences are similar to those found in two cases of hereditary hemorrhage with amyloidosis--Dutch type. The differences between vascular and plaque beta-amyloid may reflect diverse processing of the beta protein precursor in the vessel wall and brain parenchyma due to tissue-specific endopeptidases.