Cathepsin D is involved in the clearance of Alzheimer's β‐amyloid protein

Abstract

The cerebral deposition of 39–42 residue amyloid β-protein (Aβ) is a histopathological characteristic of Alzheimer's disease. The present study is aimed at finding proteinases responsible for the intracellular clearance of Aβ. The Aβ-degrading proteinase was purified from rat brain. Amino-terminal sequence analysis indicated the Aβ-degrading proteinase was cathepsin D. Purified cathepsin D hydrolyzed Aβ between Phe¹⁹ and Phe²⁰. Cathepsin D is likely to be involved in the intracellular clearance of aggregatable Aβ, since Aβ fragments with Phe²⁰ at the amino-terminus have been reported to be secreted from several lines of cultured cells.