ALZHEIMERS-DISEASE AND SOLUBLE A-BETA

The discovery of soluble amyloid beta (sA beta) suggests that the role of amyloid in Alzheimer's disease (AD) is similar to the previously studied systemic amyloidoses and alters the notion that membrane damage is the initial event in AD. The disease state is characterized by the abnormal accumulation of a normal degradative peptide, which becomes resistant to further proteolysis due to a conformational change. Mutations in the beta PP gene have been found in a very small percentage of AD cases; hence other factors, both genetic and environmental, need to be identified. Priority needs to be given to detailed studies of the structural differences between sA beta and the A beta in amyloid deposits. This will help uncover the determining factors governing the aggregation of sA beta. These structural alterations may be critical for the possible toxic effects A beta and/or associated proteins (molecular chaperones, e.g., apolipoprotein E) have on brain cell function.