Cited by 1,447Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing

Shoji, Mikio, Golde, Todd E., Ghiso, Jorge, Cheung, Tobun T., Estus, Steven, Shaffer, Lillian M., Cai, Xiao-Dan, McKay, Deborah M. +3 more·1992·Science

Abstract

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.

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Crossref · 10.1126/science.1439760

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  • Normal processing of β-APP secretes 4-kDa Aβ that is readily detected in human cerebrospinal fluid and in medium conditioned by cultured cells.

    “Recently, we and others have shown that normal processing of the large amyloid f3 protein precursor ({3-APP) secretes 4-kDa A(3 that is readily detected in human cerebrospinal fluid and in medium conditioned by cultured cells (3)(4)(5)(6).”

    From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [5]

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Authors
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., & Younkin, S. G.
Affiliations
  • Gunma University (JP)
  • Case Western Reserve University (US)
  • NYU Langone Health (US)
  • Washington University in St. Louis (US)
  • The University of Texas Southwestern Medical Center (US)
Venue
Science
Published
1992-10-02
Volume
258
Issue
5079
Pages
126-129
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2033382511
Cited by
1,447
References
32
Citations by year
2026: 4 · 2025: 6 · 2024: 16 · 2023: 13 · 2022: 13 · 2021: 18 · 2020: 23 · 2019: 16 · 2018: 18 · 2017: 15 · 2016: 37 · 2015: 26 · 2014: 28 · 2013: 38 · 2012: 37
FWCI
80.08
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG06656, R01AG006656, AG05891)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR02594)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, Alzheimer's disease, amyloid precursor protein, proteolytic processing, soluble amyloid-beta, amyloid fibrils, cerebrospinal fluid, K562 cells, neuroblastoma cells, transfection, protein secretion
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Leukemia, Myeloid, Molecular Sequence Data, Neuroblastoma, Transfection, Immunoblotting, Amyloid beta-Peptides, Amyloid beta-Protein Precursor

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