A BETA-AMYLOID PEPTIDE VARIANT RELATED WITH FAMILIAL ALZHEIMERS-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 i nvolved in the intracellular clearance of A beta (Hamazaki, H. (1996) FEBS Lett., in press). The present work shows that cathepsin D hydroly zes wild-type A beta 20 times faster than a variant A beta with a subs titution at residue 21 from Ala to Gly, Since the substitution has bee n linked to familial Alzheimer's disease and hereditary cerebral hemor rhage with amyloidosis (Hendriks et al, (1992) Nature Genet, 1, 218-22 1), the present observations suggest that the inefficient elimination of A beta by cathepsin D is capable of being one of causes of the amyl oid fibril formation.