BIOCHEMICAL-EVIDENCE FOR THE LONG-TAIL FORM (A-BETA-1-42-43) OF AMYLOID-BETA PROTEIN AS A SEED MOLECULE IN CEREBRAL DEPOSITS OF ALZHEIMERS-DISEASE

We measured the amounts of total A beta, A beta 1-40, and A beta 1-42/ 43 in brain tissues using a newly developed ELISA assay and found that the amounts of insoluble A beta 1-42/43 and insoluble A beta 1-40) we re linearly related to the amount of A beta deposits or total insolubl e A beta at their lon er and higher concentrations, respectively. In a n experiment to characterize the A beta species in brain homogenates w ith buffered saline, we unexpectedly detected soluble AB which was der ived from the insoluble amyloid deposits in brain tissue, indicating r eversible depolymerisation of AR from insoluble amyloid deposits. To c onfirm this finding, we performed 5 consecutive washes of insoluble pr ecipitates of AD brains with buffered saline. Bath species of A beta w ere found in all 5 supernatant fractions and their amounts were gradua lly decreased. The ratio of A beta 1-42/43/43 to A beta-40 was increas ed with the numbers of washes, indicating that A beta 1-42/43) existed in an exposed manner as compared to A beta 1-42/43. Thus the present finding is the first biochemical evidence that A beta 1-40, was the pr edominant species involved in the reversible exchanging reaction on se eding A beta 1-42/43 between the soluble and the insoluble forms (amyl oid fibrils). (C) 1994 Academic Press, Inc.