Predominant deposition of amyloid-beta(42(43)) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene

Amyloid (AP) deposition was investigated in cases of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis, Dutch type, due to mutations in the amyloid precursor protein (APP) gene using the end-specific monoclonal antibodies BA27 and BC05 that recognize A beta(40) or A beta(42(43)), respectively. ln cases of APP(717) mutation the predominant AP species within plaques terminate at A beta(42(43)) with relatively little A beta(40) being present. The total amount of A beta deposited as A beta(42(43)) is significantly greater than in sporadic Alzheimer's disease, consistent with the suggestion that this mutation might influence the processing of APP so as to produce more of the highly aggregatable form, A beta(1-42). In cases of APP(670/671) mutation the major peptide in plaques is also A beta(42(43)), although the proportion of plaques containing A beta(40) and the total A beta load is similar to that in sporadic Alzheimer's disease, As in sporadic Alzheimer's disease, the vascular amyloid in APP(670/671) and APP(717) and in cases of hereditary cerebral hemorrhage with amyloidosis, Dutch type is predominantly A beta(40); in this latter disorder, however, parenchymal deposits are exclusively A beta(42(43)). Although the various APP mutations may influence the type, quantity, and location of A beta deposited the predominant, and possibly the initial, species deposited in the brain parenchyma is A beta(42(43)).