Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids (original) (raw)

Nature volume 359, pages 325–327 (1992)Cite this article

Abstract

CEREBRAL deposition of the β-amyloid peptide (Aβ) is an invariant feature of Alzheimer's disease. Since the original isola-tion and characterization of αβ (ref. 1) and the subsequent cloning of its precursor protein2–5, no direct evidence for the actual production of discrete Aβ has been reported6–11. Here we investigate whether Aβ is present in human biological fluids using antibodies specific for an epitope within Aβ that spans the site of normal constitutive cleavage12,13. These antibodies were used to construct a sandwich type enzyme-linked immunosorbent assay that detects Aβ 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 Aβ and a novel Aβ fragment from human cerebrospinal fluid and conditioned medium of human mixed-brain cell cultures. These findings demonstrate that Aβ 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 Aβ.

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Author notes

  1. Michael Schiossmacher
    Present address: Institute of Neurology, Austrian Academy of Sciences, Dr Ignaz-Seipel-Platz 2, A-1010, Vienna, Austria
  2. Michael Schiossmacher and Dennis Selkoe: Department of Neurology and Program in Neurosciences, Harvard Medical School, and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
  3. Justine Whaley, Cathy Swindlehurst, Robert McCormack and Robert Wolfert: Hybritech Inc., 11095 Torreyana Road, San Diego, California 92196, USA

Authors and Affiliations

  1. Athena Neurosciences Inc., 800F Gateway Boulevard, South San Francisco, California, 94080, USA
    Peter Seubert, Carmen Vigo-Pelfrey, Fred Esch, Michael Lee, Harry Dovey, Dave Davis, Sukanto Sinha, Michael Schiossmacher, Justine Whaley, Cathy Swindlehurst, Robert McCormack, Robert Wolfert, Dennis Selkoe, Ivan Lieberburg & Dale Schenk

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  1. Peter Seubert
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  2. Carmen Vigo-Pelfrey
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  3. Fred Esch
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  4. Michael Lee
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  5. Harry Dovey
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  6. Dave Davis
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  7. Sukanto Sinha
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  8. Michael Schiossmacher
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  9. Justine Whaley
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  10. Cathy Swindlehurst
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  11. Robert McCormack
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  12. Robert Wolfert
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  13. Dennis Selkoe
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  14. Ivan Lieberburg
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  15. Dale Schenk
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Seubert, P., Vigo-Pelfrey, C., Esch, F. et al. Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids.Nature 359, 325–327 (1992). https://doi.org/10.1038/359325a0

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