PMID- 1406936 OWN - NLM STAT- MEDLINE DCOM- 19921028 LR - 20220321 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 359 IP - 6393 DP - 1992 Sep 24 TI - Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. PG - 325-7 AB - Cerebral deposition of the beta-amyloid peptide (A beta) is an invariant feature of Alzheimer's disease. Since the original isolation and characterization of A beta (ref. 1) and the subsequent cloning of its precursor protein, no direct evidence for the actual production of discrete A beta has been reported. Here we investigate whether A beta is present in human biological fluids using antibodies specific for an epitope within A beta that spans the site of normal constitutive cleavage. These antibodies were used to construct a sandwich-type enzyme-linked immunosorbent assay that detects A beta in cerebrospinal fluid, plasma and conditioned medium of human mixed-brain cells grown in vitro (see also ref. 14). By affinity chromatography, we have purified and sequenced A beta and a novel A beta fragment from human cerebrospinal fluid and conditioned medium of human mixed-brain cell cultures. These findings demonstrate that A beta is produced and released both in vivo and in vitro. These observations offer new opportunities for developing diagnostic tests for Alzheimer's disease and therapeutic strategies aimed at reducing the cerebral deposition of A beta. FAU - Seubert, P AU - Seubert P AD - Athena Neurosciences Inc., South San Francisco, California 94080. FAU - Vigo-Pelfrey, C AU - Vigo-Pelfrey C FAU - Esch, F AU - Esch F FAU - Lee, M AU - Lee M FAU - Dovey, H AU - Dovey H FAU - Davis, D AU - Davis D FAU - Sinha, S AU - Sinha S FAU - Schlossmacher, M AU - Schlossmacher M FAU - Whaley, J AU - Whaley J FAU - Swindlehurst, C AU - Swindlehurst C AU - et al. LA - eng PT - Journal Article PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Antibodies, Monoclonal) RN - 0 (Peptide Fragments) SB - IM CIN - Nature. 1992 Sep 24;359(6393):268-9. PMID: 1406927 MH - Alzheimer Disease/*metabolism MH - Amino Acid Sequence MH - Amyloid beta-Peptides/analysis/*isolation & purification MH - Amyloid beta-Protein Precursor/isolation & purification MH - Antibodies, Monoclonal MH - Brain/*metabolism MH - Cells, Cultured MH - Cross Reactions MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Molecular Sequence Data MH - Peptide Fragments/isolation & purification MH - Radioimmunoassay MH - Solubility 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 - 10.1038/359325a0 [doi] PST - ppublish SO - Nature. 1992 Sep 24;359(6393):325-7. doi: 10.1038/359325a0.