ALZHEIMERS BETA-AMYLOID PEPTIDE SPECIFICALLY INTERACTS WITH AND IS DEGRADED BY INSULIN DEGRADING ENZYME

Cerebral deposition of beta-amyloid peptide (beta A) is a hallmark of Alzheimer's disease. Concentration of beta A could play a critical rol e in the rate of amyloid deposition. It is therefore of considerable i mportance to identify proteases involved in processing of beta A. I-12 5-labeled synthetic beta A specifically cross-linked to a single prote in with M(r) = 110,000 in cytosol fractions from rat brain and liver. This protein was identified as insulin degrading enzyme (IDE) since th e labeling of the 110 kDa protein was completely blocked by an excess of insulin, and anti-IDE monoclonal antibodies precipitated the labele d protein. Purified rat IDE effectively degraded beta A.