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| AMYLOID BETA-PEPTIDE IS PRODUCED BY CULTURED-CELLS DURING NORMAL METABOLISM |
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| Author(s): HAASS C, SCHLOSSMACHER MG, HUNG AY, VIGOPELFREY C, MELLON A, OSTASZEWSKI BL, LIEBERBURG I, KOO EH, SCHENK D, TEPLOW DB, SELKOE DJ |
| Source: NATURE Volume: 359 Issue: 6393 Pages: 322-325 Published: SEP 24 1992 |
| Times Cited: 1,202 References: 20 |
| Abstract: ALZHEIMER's disease is characterized by the extracellular deposition in the brain and its blood vessels of insoluble aggregates of the amyloid beta-peptide (A-beta), a fragment, of about 40 amino acids in length, of the integral membrane protein beta-amyloid precursor protein (beta-APP)1. The mechanism of extracellular accumulation of A-beta in brain is unknown and no simple in vitro or in vivo model systems that produce extracellular A-beta have been described. We report here the unexpected identification of the 4K (M(r) 4,000) A-beta and a truncated form of A-beta (approximately 3K) in media from cultures of primary cells and untransfected and beta-APP-transfected cell lines grown under normal conditions. These peptides were immunoprecipitated readily from culture medium by A-beta-specific antibodies and their identities confirmed by sequencing. The concept that pathological processes are responsible for the production of A-beta must now be reassessed in light of the observation that A-beta is produced in soluble form in vitro and in vivo2 during normal cellular metabolism. Further, these findings provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A-beta, the primary protein constituent of the senile plaques of Alzheimer's disease. |
| Document Type: Article |
| Language: English |
| Reprint Address: HAASS, C (reprint author), HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02155 USA |
Addresses:
1. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02155 USA
2. BRIGHAM & WOMENS HOSP, CTR NEUROL DIS, DEPT MED NEUROL, BOSTON, MA 02155 USA
3. ATHENA NEUROSCI INC, S SAN FRANCISCO, CA 94090 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: JP503 |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |