The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Alzheimer's-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal
Open accessAbstract
It now appears likely that soluble oligomers of amyloid-beta1-42 peptide, rather than insoluble fibrils, act as the primary neurotoxin in Alzheimer's disease (AD). Consequently, compounds capable of altering the assembly state of these oligomers (referred to as ADDLs) may have potential for AD therapeutics. Phenolic compounds are of particular interest for their ability to disrupt Abeta oligomerization and reduce pathogenicity. This study has focused on oleocanthal (OC), a naturally-occurring phenolic compound found in extra-virgin olive oil. OC increased the immunoreactivity of soluble Abeta species, when assayed with both sequence- and conformation-specific Abeta antibodies, indicating changes in oligomer structure. Analysis of oligomers in the presence of OC showed an upward shift in MW and a ladder-like distribution of SDS-stable ADDL subspecies. In comparison with control ADDLs, oligomers formed in the presence of OC (Abeta-OC) showed equivalent colocalization at synapses but exhibited greater immunofluorescence as a result of increased antibody recognition. The enhanced signal at synapses was not due to increased synaptic binding, as direct detection of fluorescently-labeled ADDLs showed an overall reduction in ADDL signal in the presence of OC. Decreased binding to synapses was accompanied by significantly less synaptic deterioration assayed by drebrin loss. Additionally, treatment with OC improved antibody clearance of ADDLs. These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“And in fact, not all oligomers are toxic, even those oligomers of a given size. Subtle conformation changes affect toxicity and immunoreactivity (Chromy et al., 2003; Pitt et al., 2009).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Pitt et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 1×
“…neurons in much greater abundance than ADDLs b50 kDa (Lacor et al., 2007); Aβ⁎56 has been identified as the major toxic species in Tg2576 mice (Lesne et al., 2006), although there is evidence that smaller oAβs are capable of producing functional alterations in neuronal functioning (Walsh…”
BackgroundRetractedThe 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
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
A guided tour into subcellular colocalization analysis in light microscopy
Bolte, S., & Cordelières, F. P. (2006) · Journal of Microscopy · doi:10.1111/j.1365-2818.2006.01706.x · Cited by 5,506
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Self-citationYang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautschy, S. A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m404751200 · Cited by 2,336
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012
Cited by
Sorted by citations
Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis
Viola, K. L., & Klein, W. L. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1386-3 · Cited by 628
Self-citationBiochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer DiseasePreprint
Masters, C. L., & Selkoe, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006262 · Cited by 554
Antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil
Cicerale, S., Lucas, L., & Keast, R. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2011.09.006 · Cited by 483
Biological Activities of Phenolic Compounds Present in Virgin Olive Oil
Cicerale, S., Lucas, L., & Keast, R. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11020458 · Cited by 467
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442
Metadata
- Authors
- Pitt, J., Roth, W., Lacor, P., Smith, A. B., Blankenship, M., Velasco, P., De Felice, F., Breslin, P., & Klein, W. L.
- Affiliations
- Northwestern University (US)
- Monell Chemical Senses Center (US)
- Western Illinois University (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Pitt, Jason
- Breslin, Paul
- Klein, William L.
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 240
- Issue
- 2
- Pages
- 189-197
- ISSN
- 0041-008X (ISSN-L)
- PMC
- PMC2808212
- OpenAlex
- W2025825556
- Cited by
- 134
- References
- 53
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 11 · 2018: 12 · 2017: 13 · 2016: 9 · 2015: 10 · 2014: 5 · 2013: 15 · 2012: 17
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institutes of Health (5p50dc006760-05, 5t32ag020418-08)
- National Institute on Aging (5 T32 AG020418, R01AG022547, R01AG029460, T32-AG020418)
- National Institute on Deafness and Other Communication Disorders (P50 DC06760, P50-DC006760)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta oligomers, oleocanthal, extra virgin olive oil, phenolic compounds, synaptotoxicity, oligomerization, immunoreactivity, drebrin, antibody clearance, neuroprotection, Alzheimer's disease therapeutics
- MeSH terms
- Cyclopentane Monoterpenes, Aldehydes, Animals, Antibodies, Antigen-Antibody Reactions, Cells, Cultured, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, Hippocampus, Humans, Molecular Weight, Neuropeptides, Peptide Fragments, Phenols, Protein Conformation, Synapses, Immunoblotting, Amyloid beta-Peptides, Microscopy, Confocal, Neuroprotective Agents, Protein Multimerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
