Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing

DOI Web Site 31 Citations
  • Mikio Shoji
    Department of Neurology, Gunma University, Gunma 371, Japan..
  • Todd E. Golde
    Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
  • Jorge Ghiso
    Department of Pathology, New York University Medical Center, New York, NY 10016.
  • Tobun T. Cheung
    Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
  • Steven Estus
    Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110.
  • Lillian M. Shaffer
    Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
  • Xiao-Dan Cai
    Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
  • Deborah M. McKay
    Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
  • Ron Tintner
    Department of Neurology and the Alzheimer's Disease Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235.
  • Bias Frangione
    Department of Pathology, New York University Medical Center, New York, NY 10016.
  • Steven G. Younkin
    Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.

Abstract

<jats:p>The 4-kilodalton (39 to 43 amino acids) amyloid β protein (βAP), which is deposited as amyloid in the brains of patients with Alzheimer's disease, is derived from a large protein, the amyloid β protein precursor (βAPP). Human mononuclear leukemic (K562) cells expressing a βAP-bearing, carboxyl-terminal βAPP derivative released significant amounts of a soluble 4-kilodalton βAPP derivative essentially identical to the βAP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length βAPP and M17 cells expressing only endogenous βAPP also released soluble 4-kilodalton βAP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton βAP that is essentially identical to the 4-kilodalton βAP deposited as insoluble amyloid fibrils in Alzheimer's disease.</jats:p>

Journal

  • Science

    Science 258 (5079), 126-129, 1992-10-02

    American Association for the Advancement of Science (AAAS)

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