Previous studies on the purification and characterization of the predominant extracellular Aβ degrading activity in the murine BV-2 microglial cell line demonstrated that insulin-degrading enzyme (IDE) or a novel protease indistinguishable from IDE was responsible for this activity. In an extension of this work Kostas Vekrellis (122.11) reported that differentiated PC-12 cells and primary rat cortical cultures also possessed an Aβ-degrading activity that could be competitively inhibited by addition of insulin or glucagon, and that this activity was cell associated. Moreover, transfection of CHO cells (already overexpressing APP) with wtIDE caused a dramatic decrease in the Aβ present in the conditioned media of these cells, whereas transfection with mutant IDE had no such effect. Furthermore, immunohistochemical studies of AD brain indicated that IDE was increased within neurons proximate to amyloid plaques.—Dominic Walsh


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