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

[hereditary cerebral hemorrhage with amyloidosis]

The cerebral deposition of 40 -42 residue amyloid beta -protein (Abeta ) is a characteristic of Alzheimer 's disease . Cathepsin D is possibly involved in the intracellular clearance of Abeta (Hamazaki , H . (1996 ) FEBS Lett ., in press ). The present work shows that cathepsin D hydrolyzes wild-type Abeta 20 times faster than a variant Abeta 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 Abeta by cathepsin D is capable of being one of causes of the amyloid fibril formation .

Diseases
Validation

Diseases presenting "cerebral deposition" symptom

hereditary cerebral hemorrhage with amyloidosis

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