The cerebral deposition of 39-42 residue amyloid beta-protein (A beta)
is a histopathological characteristic of Alzheimer's disease. The pre
sent study is aimed at finding proteinases responsible for the intrace
llular clearance of A beta. The A beta degrading proteinase was purifi
ed from rat brain. Aminoterminal sequence analysis indicated the A bet
a-degrading proteinase was cathepsin D. Purified cathepsin D hydrolyze
d A beta between Phe(19) and Phe(20). Cathepsin D is likely to be invo
lved in the intracellular clearance of aggregatable A beta, since A be
ta fragments with Phe(20) at the amino-terminus have been reported to
be secreted from several lines of cultured cells.