The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Amyloid β-peptide is produced by cultured cells during normal metabolism
Abstract
Alzheimer's disease is characterized by the extracellular deposition in the brain and its blood vessels of insoluble aggregates of the amyloid beta-peptide (A beta), a fragment, of about 40 amino acids in length, of the integral membrane protein beta-amyloid precursor protein (beta-APP). The mechanism of extracellular accumulation of A beta in brain is unknown and no simple in vitro or in vivo model systems that produce extracellular A beta have been described. We report here the unexpected identification of the 4K (M(r) 4,000) A beta and a truncated form of A beta (approximately 3K) in media from cultures of primary cells and untransfected and beta-APP-transfected cell lines grown under normal conditions. These peptides were immunoprecipitated readily from culture medium by A beta-specific antibodies and their identities confirmed by sequencing. The concept that pathological processes are responsible for the production of A beta must not be reassessed in light of the observation that A beta is produced in soluble form in vitro and in vivo during normal cellular metabolism. Further, these findings provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A beta, the primary protein constituent of the senile plaques of 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).”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [4]
In the citing paper
“High BACE1 enzymatic activity was found in human AD brain extracts, which is consistent with the finding that neurons produce the highest levels of Aβ (3,45).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [45]
Citations
Cites
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Self-citationCleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor
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Self-citationAmyloid β-protein deposition in tissues other than brain in Alzheimer's disease
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Self-citationPotentially Amyloidogenic, Carboxyl-Terminal Derivatives of the Amyloid Protein Precursor
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Self-citation
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Sorted by citations
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Self-citationThe amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164
Self-citationAlzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Self-citationSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
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Metadata
- Authors
- Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., & Selkoe, D. J.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Nature
- Published
- 1992-09
- Volume
- 359
- Issue
- 6393
- Pages
- 322-325
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1979543098
- Cited by
- 1,921
- References
- 17
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 22 · 2023: 15 · 2022: 19 · 2021: 28 · 2020: 31 · 2019: 25 · 2018: 29 · 2017: 35 · 2016: 43 · 2015: 46 · 2014: 51 · 2013: 43 · 2012: 67
- FWCI
- 80.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- 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, amyloid plaques, cell culture model, drug screening
- MeSH terms
- Antibodies, Epitopes, Cell Line, DNA, Humans, Kidney, Methionine, Molecular Weight, Recombinant Proteins, Transfection, Amyloid beta-Peptides, Amyloid beta-Protein Precursor
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