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| AN INCREASED PERCENTAGE OF LONG AMYLOID-BETA PROTEIN SECRETED BY FAMILIAL AMYLOID-BETA PROTEIN-PRECURSOR (BETA-APP(717)) MUTANTS |
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| Author(s): SUZUKI N, CHEUNG TT, CAI XD, ODAKA A, OTVOS L, ECKMAN C, GOLDE TE, YOUNKIN SG |
| Source: SCIENCE Volume: 264 Issue: 5163 Pages: 1336-1340 Published: MAY 27 1994 |
| Times Cited: 1,015 References: 49 |
| Abstract: Normal processing of the amyloid beta protein precursor (beta APP) results in secretion of a soluble 4-kilodalton protein essentially identical to the amyloid beta protein (A beta) that forms insoluble fibrillar deposits in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or the beta APP(717) mutants linked to familial Alzheimer's disease were compared by (i) isolation of metabolically labeled 4-kilodalton A beta from conditioned medium, digestion with cyanogen bromide, and analysis of the carboxyl-terminal peptides released, or (ii) analysis of the A beta in conditioned medium with sandwich enzyme-linked immunosorbent assays that discriminate Ap(1-40) from the longer AP(1-42). Both methods demonstrated that the 4-kilodalton Ap released from wild-type beta APP is primarily but not exclusively AP(1-40). The beta APP(717) mutations, which are located th ree residues carboxyl to A beta(43), consistently caused a 1.5- to 1.9-fold increase in the percentage of longer A beta generated. Long A beta (for example, A beta(1-42)) forms insoluble amyloid fibrils more rapidly than Ap(1-40). Thus, the beta APP(717) mutants may cause Alzheimer's disease because they secrete increased amounts of long A beta, thereby fostering amyloid deposition. |
| Document Type: Article |
| Language: English |
Addresses:
1. CASE WESTERN RESERVE UNIV, INST PATHOL, DIV NEUROPATHOL, CLEVELAND, OH 44106 USA
2. TAKEDA CHEM IND LTD, DIV DISCOVERY RES, TSUKUBA, IBARAKI 30042 JAPAN
3. WISTAR INST ANAT & BIOL, PHILADELPHIA, PA 19104 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: NN767 |
| ISSN: 0036-8075 |
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