PMID- 1383826
OWN - NLM
STAT- MEDLINE
DCOM- 19921028
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 359
IP  - 6393
DP  - 1992 Sep 24
TI  - Amyloid beta-peptide is produced by cultured cells during normal metabolism.
PG  - 322-5
AB  - 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). 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 not be reassessed in light of the observation that A beta is produced in 
      soluble form in vitro and in vivo 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.
FAU - Haass, C
AU  - Haass C
AD  - Department of Neurology and Program in Neuroscience, Harvard Medical School, 
      Boston, Massachusetts 02155.
FAU - Schlossmacher, M G
AU  - Schlossmacher MG
FAU - Hung, A Y
AU  - Hung AY
FAU - Vigo-Pelfrey, C
AU  - Vigo-Pelfrey C
FAU - Mellon, A
AU  - Mellon A
FAU - Ostaszewski, B L
AU  - Ostaszewski BL
FAU - Lieberburg, I
AU  - Lieberburg I
FAU - Koo, E H
AU  - Koo EH
FAU - Schenk, D
AU  - Schenk D
FAU - Teplow, D B
AU  - Teplow DB
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antibodies)
RN  - 0 (Epitopes)
RN  - 0 (Recombinant Proteins)
RN  - 9007-49-2 (DNA)
RN  - AE28F7PNPL (Methionine)
SB  - IM
CIN - Nature. 1992 Sep 24;359(6393):268-9. PMID: 1406927
MH  - Amyloid beta-Peptides/*biosynthesis/genetics/isolation & purification
MH  - Amyloid beta-Protein Precursor/*biosynthesis/genetics/isolation & purification
MH  - Antibodies
MH  - Cell Line
MH  - DNA/genetics
MH  - Epitopes/analysis
MH  - Humans
MH  - Kidney
MH  - Methionine/metabolism
MH  - Molecular Weight
MH  - Recombinant Proteins/biosynthesis/isolation & purification
MH  - Transfection
EDAT- 1992/09/24 00:00
MHDA- 1992/09/24 00:01
CRDT- 1992/09/24 00:00
PHST- 1992/09/24 00:00 [pubmed]
PHST- 1992/09/24 00:01 [medline]
PHST- 1992/09/24 00:00 [entrez]
AID - 10.1038/359322a0 [doi]
PST - ppublish
SO  - Nature. 1992 Sep 24;359(6393):322-5. doi: 10.1038/359322a0.