The DOI matches its Crossref record; 69 of the 71 references it cites were found in a registry or an index.
Oligomeric and Fibrillar Species of Amyloid-β Peptides Differentially Affect Neuronal Viability
Open accessAbstract
Genetic evidence predicts a causative role for amyloid-beta (A beta) in Alzheimer's disease. Recent debate has focused on whether fibrils (amyloid) or soluble oligomers of A beta are the active species that contribute to neurodegeneration and dementia. We developed two aggregation protocols for the consistent production of stable oligomeric or fibrillar preparations of A beta-(1-42). Here we report that oligomers inhibit neuronal viability 10-fold more than fibrils and approximately 40-fold more than unaggregated peptide, with oligomeric A beta-(1-42)-induced inhibition significant at 10 nm. Under A beta-(1-42) oligomer- and fibril-forming conditions, A beta-(1-40) remains predominantly as unassembled monomer and had significantly less effect on neuronal viability than preparations of A beta-(1-42). We applied the aggregation protocols developed for wild type A beta-(1-42) to A beta-(1-42) with the Dutch (E22Q) or Arctic (E22G) mutations. Oligomeric preparations of the mutations exhibited extensive protofibril and fibril formation, respectively, but were not consistently different from wild type A beta-(1-42) in terms of inhibition of neuronal viability. However, fibrillar preparations of the mutants appeared larger and induced significantly more inhibition of neuronal viability than wild type A beta-(1-42) fibril preparations. These data demonstrate that protocols developed to produce oligomeric and fibrillar A beta-(1-42) are useful in distinguishing the structural and functional differences between A beta-(1-42) and A beta-(1-40) and genetic mutations of A beta-(1-42).
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In the citing paper
“In addition, the MOAB-2-based oA42 ELISA detects oligomeric but not monomeric A42 using synthetic preparations characterized previously by our laboratory (data not shown) (47,48).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [47]
In the citing paper
“The 48 h total incubation leads to mature Aβ42 fibrils, as observed by TEM (Figure 10, panel a) while the Western blot shows the presence of higher order Aβ42 oligomers (Figure 10, lane a), likely due to an assembly-disassembly equilibrium that is established for mature Aβ fibrils.89–91”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [90]
In the citing paper
“However, this approach may not be optimal for the Aβ42 peptide, given the increased toxicity observed for the soluble Aβ42 oligomers.90”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [90]
In the citing paper
“Finally, in neurons, PCSK9 overexpression led to a worsening of neurotoxicity induced by different aggregation forms of Aβ, which have previously been demonstrated to have toxic effects in these cells [31,52].”
From PCSK9 affects astrocyte cholesterol metabolism and reduces neuron cholesterol supplying in vitro: potential implications in Alzheimer’s disease (2022) · cites this paper as [52]
In the citing paper
“All A preparations used were similar to those characterized previously (24) in that they contain monomers and oligomers of A but do not contain fibrils (see supplemental Fig. 1, A and B).”
From Internalization of β-Amyloid Peptide by Primary Neurons in the Absence of Apolipoprotein E (2007) · cites this paper as [24]
Citations
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Self-citationNeurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides
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Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
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Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938
Caughey, B., & Lansbury, P. T. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.010302.081142 · Cited by 1,650
Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways
Bitan, G., Kirkitadze, M. D., Lomakin, A., Vollers, S. S., Benedek, G. B., & Teplow, D. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222681699 · Cited by 1,316
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168
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Metadata
- Authors
- Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J.
- Affiliations
- Northwestern University (US)
- Corresponding author
- LaDu, Mary Jo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 277
- Issue
- 35
- Pages
- 32046-32053
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2168025729
- Cited by
- 1,452
- References
- 71
- Citations by year
- 2026: 25 · 2025: 33 · 2024: 40 · 2023: 46 · 2022: 45 · 2021: 47 · 2020: 49 · 2019: 55 · 2018: 65 · 2017: 58 · 2016: 61 · 2015: 70 · 2014: 78 · 2013: 86 · 2012: 86
- FWCI
- 22.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- 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 oligomers, amyloid fibrils, Alzheimer's disease, neuronal viability, peptide aggregation, protofibrils, neurotoxicity
- MeSH terms
- Alzheimer Disease, Cell Survival, Humans, Neuroblastoma, Neurons, Peptide Fragments, Tumor Cells, Cultured, Amyloid beta-Peptides, Microscopy, Atomic Force
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