A beta-amyloid peptide variant related with familial Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis is poorly eliminated by cathepsin D

The cerebral deposition of 40-42 residue amyloid beta-protein (A beta) is a characteristic of Alzheimer's disease, Cathepsin D is possibly involved in the intracellular clearance of A beta (Hamazaki, H. (1996) FEBS Lett., in press). The present work shows that cathepsin D hydrolyzes wild-type A beta 20 times faster than a variant A beta with a substitution at residue 21 from Ala to Gly, Since the substitution has been linked to familial Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Hendriks et al, (1992) Nature Genet, 1, 218-221), the present observations suggest that the inefficient elimination of A beta by cathepsin D is capable of being one of causes of the amyloid fibril formation.