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 s tudied 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. Mutat ions in the beta PP gene have been found in a very small percentage of AD cases; hence other factors, both genetic and environmental, need t o be identified. Priority needs to be given to detailed studies of the structural differences between sA beta and the A beta in amyloid depo sits. This will help uncover the determining factors governing the agg regation of sA beta. These structural alterations may be critical for the possible toxic effects A beta and/or associated proteins (molecula r chaperones, e.g., apolipoprotein E) have on brain cell function.