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Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
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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“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).”
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Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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