The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.
Detection of a Novel Intraneuronal Pool of Insoluble Amyloid β Protein that Accumulates with Time in Culture
Open accessAbstract
The amyloid-β peptide (Aβ) is produced at several sites within cultured human NT2N neurons with Aβ1-42 specifically generated in the endoplasmic reticulum/intermediate compartment. Since Aβ is found as insoluble deposits in senile plaques of the AD brain, and the Aβ peptide can polymerize into insoluble fibrils in vitro, we examined the possibility that Aβ1-40, and particularly the more highly amyloidogenic Aβ1-42, accumulate in an insoluble pool within NT2N neurons. Remarkably, we found that formic acid extraction of the NT2N cells solubilized a pool of previously undetectable Aβ that accounted for over half of the total intracellular Aβ. Aβ1-42 was more abundant than Aβ1-40 in this pool, and most of the insoluble Aβ1-42 was generated in the endoplasmic reticulum/intermediate compartment pathway. High levels of insoluble Aβ were also detected in several nonneuronal cell lines engineered to overexpress the amyloid-β precursor protein. This insoluble intracellular pool of Aβ was exceptionally stable, and accumulated in NT2N neurons in a time-dependent manner, increasing 12-fold over a 7-wk period in culture. These novel findings suggest that Aβ amyloidogenesis may be initiated within living neurons rather than in the extracellular space. Thus, the data presented here require a reexamination of the prevailing view about the pathogenesis of Aβ deposition in the AD brain.
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“The amyloid cascade hypothesis predicts that a gradual increase of A-(1-42) levels in brain interstitial fluid (3,4) may lead to A oligomerization and eventually to A fibrillization (5).”
From Internalization of β-Amyloid Peptide by Primary Neurons in the Absence of Apolipoprotein E (2007) · cites this paper as [3]
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“Subsequent work showed that particularly the disease-linked Aβ42 peptide, rather than the more abundantly secreted Aβ40 peptide, increased with differentiation and time in culture within clonal NT2 cells that can develop a neuron-like phenotype [174, 195].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [174]
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Cites
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Flagged first, then by citations
1 of the 36 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Kim, 1988, Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide, Neurosci Res Commun, 2, 121
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Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
Translating cell biology into therapeutic advances in Alzheimer's disease
Selkoe, D. J. (1999) · Nature · doi:10.1038/399a023 · Cited by 1,166
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207
Metadata
- Authors
- Skovronsky, D. M., Doms, R. W., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- ORCID
- Lee, Virginia M.-Y.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1998-05-18
- Volume
- 141
- Issue
- 4
- Pages
- 1031-1039
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2132781
- OpenAlex
- W2130792655
- Cited by
- 290
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 3 · 2019: 8 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 6 · 2014: 3 · 2013: 8 · 2012: 8
- FWCI
- 15.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- 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, amyloid-beta 42, Aβ40, endoplasmic reticulum, amyloidogenesis, Alzheimer's disease, amyloid plaques, amyloid precursor protein overexpression, formic acid extraction
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Line, Endoplasmic Reticulum, Genetic Vectors, Cricetinae, Humans, Neurons, Peptide Fragments, Recombinant Proteins, Semliki forest virus, Solubility, Subcellular Fractions, Transfection, Tumor Cells, Cultured, Amyloid beta-Peptides, CHO Cells, Carcinoma, Embryonal
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