A BETA-AMYLOID PEPTIDE VARIANT RELATED WITH FAMILIAL ALZHEIMERS-DISEASE AND HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS IS POORLY ELIMINATED BY CATHEPSIN-D
H. Hamazaki, A BETA-AMYLOID PEPTIDE VARIANT RELATED WITH FAMILIAL ALZHEIMERS-DISEASE AND HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS IS POORLY ELIMINATED BY CATHEPSIN-D, FEBS letters, 397(2-3), 1996, pp. 313-315
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.