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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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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