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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.
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“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
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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RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory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
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397
Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization
Orgogozo, J.-M., Gilman, S., Dartigues, J.-F., Laurent, B., Puel, M., Kirby, L. C., Jouanny, P., Dubois, B., Eisner, L., Flitman, S., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000073623.84147.a8 · Cited by 1,356
Lacor, P. N., Buniel, M. C., Furlow, P. W., Sanz Clemente, A., Velasco, P. T., Wood, M., Viola, K. L., & Klein, W. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3501-06.2007 · Cited by 1,188
Self-citationDietary Intake of Antioxidants and Risk of Alzheimer Disease
Engelhart, M. J. (2002) · JAMA · doi:10.1001/jama.287.24.3223 · Cited by 1,080
Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers
Lacor, P. N., Buniel, M. C., Chang, L., Fernandez, S. J., Gong, Y., Viola, K. L., Lambert, M. P., Velasco, P. T., Bigio, E. H., Finch, C. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3432-04.2004 · Cited by 954
Self-citationIbuprofen-like activity in extra-virgin olive oil
Beauchamp, G. K., Keast, R. S. J., Morel, D., Lin, J., Pika, J., Han, Q., Lee, C.-H., Smith, A. B., & Breslin, P. A. S. (2005) · Nature · doi:10.1038/437045a · Cited by 885
De Felice, F. G., Velasco, P. T., Lambert, M. P., Viola, K., Fernandez, S. J., Ferreira, S. T., & Klein, W. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607483200 · Cited by 882
Self-citationGeorganopoulou, D. G., Chang, L., Nam, J.-M., Thaxton, C. S., Mufson, E. J., Klein, W. L., & Mirkin, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409336102 · Cited by 835
Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease
Jacobsen, J. S., Wu, C.-C., Redwine, J. M., Comery, T. A., Arias, R., Bowlby, M., Martone, R., Morrison, J. H., Pangalos, M. N., Reinhart, P. H., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600948103 · Cited by 701
De Felice, F. G., Vieira, M. N. N., Bomfim, T. R., Decker, H., Velasco, P. T., Lambert, M. P., Viola, K. L., Zhao, W.-Q., Ferreira, S. T., & Klein, W. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809158106 · Cited by 657 · cited 1×
“Changes in ADDL binding sites have also been recently reported (De Felice et al., 2009).”
BackgroundWang, H.-W., Pasternak, J. F., Kuo, H., Ristic, H., Lambert, M. P., Chromy, B., Viola, K. L., Klein, W. L., Stine, W. B., Krafft, G. A., et al. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03058-x · Cited by 527
Antiparallel β-sheet: a signature structure of the oligomeric amyloid β-peptide
Cerf, E., Sarroukh, R., Tamamizu‐Kato, S., Breydo, L., Derclaye, S., Dufrêne, Y. F., Narayanaswami, V., Goormaghtigh, E., Ruysschaert, J., & Raussens, V. (2009) · Biochemical Journal · doi:10.1042/bj20090379 · Cited by 511
Deshpande, A. M., Mina, E. W., Glabe, C. G., & Busciglio, J. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1189-06.2006 · Cited by 508
Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers
De Felice, F. G., Wu, D., Lambert, M. P., Fernandez, S. J., Velasco, P. T., Lacor, P. N., Bigio, E. H., Jerecic, J., Acton, P. J., Shughrue, P. J., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.029 · Cited by 432
Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M. P., Klein, W. L., Link, C. D., & Luo, Y. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3448-06.2006 · Cited by 418
Sengupta, A., Kabat, J., Novak, M., Wu, Q., Grundke-Iqbal, I., & Iqbal, K. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0813 · Cited by 363
Structural Characterization of a Soluble Amyloid β-Peptide Oligomer
Yu, L. P., Edalji, R. P., Harlan, J. E., Holzman, T. F., López, A. R., Labkovsky, B., Hillen, H., Barghorn, S., Ebert, U., Richardson, P. L., et al. (2009) · Biochemistry · doi:10.1021/bi802046n · Cited by 360
Wang, J., Ho, L., Zhao, W., Ono, K., Rosensweig, C., Chen, L., Humala, N., Teplow, D. B., & Pasinetti, G. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0364-08.2008 · Cited by 360
Vaccination with soluble Aβ oligomers generates toxicity‐neutralizing antibodies
Lambert, M. P., Viola, K. L., Chromy, B. A., Chang, L., Morgan, T. E., Yu, J., Venton, D. L., Krafft, G. A., Finch, C. E., & Klein, W. L. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00592.x · Cited by 349
Self-citationMonoclonal antibodies that target pathological assemblies of Aβ
Lambert, M. P., Velasco, P. T., Chang, L., Viola, K. L., Fernandez, S., Lacor, P. N., Khuon, D., Gong, Y., Bigio, E. H., Shaw, P., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04157.x · Cited by 314
Solfrizzi, V., Colacicco, A. M., D’Introno, A., Capurso, C. A., Torres, F., Rizzo, C., Capurso, A., & Panza, F. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.026 · Cited by 262
Takahashi, H., Sekino, Y., Tanaka, S., Mizui, T., Kishi, S., & Shirao, T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-16-06586.2003 · Cited by 237
Ibuprofen reduces Aβ, hyperphosphorylated tau and memory deficits in Alzheimer mice
McKee, A. C., Carreras, I., Hossain, L., Ryu, H., Klein, W. L., Oddo, S., LaFerla, F. M., Jenkins, B. G., Kowall, N. W., & Dedeoglu, A. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.095 · Cited by 201
Targeting the neurotoxic species in Alzheimer's disease: inhibitors of Aβ oligomerization
Felice, F. G. D., Vieira, M. N. N., Saraiva, L. M., Figueroa‐Villar, J. D., Garcia-Abreu, J., Liu, R., Chang, L., Klein, W. L., & Ferreira, S. T. (2004) · The FASEB Journal · doi:10.1096/fj.04-1764com · Cited by 196
Effects of Grape Seed-derived Polyphenols on Amyloid β-Protein Self-assembly and Cytotoxicity*
Ono, K., Condron, M. M., Ho, L., Wang, J., Zhao, W., Pasinetti, G. M., & Teplow, D. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806154200 · Cited by 190
Durairajan, S. S. K., Yuan, Q., Xie, L., Chan, W. S., Kum, W.-F., Koo, I., Liu, C., Song, Y., Huang, J., Klein, W. L., et al. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.09.006 · Cited by 149
Ho, L., Chen, L. H., Wang, J., Zhao, W., Talcott, S. T., Ono, K., Teplow, D. B., Humala, N., Cheng, A., Percival, S. S., et al. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0916 · Cited by 127
Knobloch, M., Farinelli, M., Konietzko, U., Nitsch, R. M., & Mansuy, I. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0395-07.2007 · Cited by 121
Aoki, C. J., Sekino, Y., Hanamura, K., Fujisawa, S., Mahadomrongkul, V., Ren, Y., & Shirao, T. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20449 · Cited by 119
Höck, C., Maddalena, A. S., Raschig, A., Müller-Spahn, F., Eschweiler, G. W., Huger, K., Hewer, I., Hampel, H. J., Müller-Thornsen, T., Oertel, W. H., et al. (2003) · Amyloid · doi:10.3109/13506120308995249 · Cited by 110
Ivanov, A., Esclapez, M., Pellegrino, C., Shirao, T., & Ferhat, L. (2009) · Journal of Cell Science · doi:10.1242/jcs.033464 · Cited by 109
Smith, A. B., Han, Q., Breslin, P. A. S., & Beauchamp, G. K. (2005) · Organic Letters · doi:10.1021/ol052106a · Cited by 100
Why Alzheimer's is a disease of memory: The attack on synapses by Aß oligomers (ADDLs)
Viola, K. L., Velasco, P. T., & Klein, W. L. (2008) · The journal of nutrition health & aging · doi:10.1007/bf02982587 · Cited by 97
Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells
Blasko, I., Apochal, A., Boeck, G., Hartmann, T., Grubeck‐Loebenstein, B., & Ransmayr, G. N. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0451 · Cited by 92
Bazoti, F. N., Bergquist, J., Markides, K. E., & Tsarbopoulos, A. (2006) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2005.11.016 · Cited by 88
Oxidative damage in brain from human mutant APP/PS-1 double knock-in mice as a function of age
Abdul, H. M., Rukhsana Sultana, A., Clair, D. K. S., Markesbery, W. R., & Butterfield, D. A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.08.012 · Cited by 81
Anker, J. N., Hall, W. P., Lambert, M. P., Velasco, P. T., Mrksich, M., Klein, W. L., & Duyne, R. P. V. (2009) · The Journal of Physical Chemistry C · doi:10.1021/jp900266k · Cited by 48
Bazoti, F. N., Bergquist, J., Markides, K. E., & Tsarbopoulos, A. (2008) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2008.03.011 · Cited by 43
Is passive immunization for Alzheimer's disease ‘alive and well’ or ‘dead and buried’?
Jicha, G. A. (2009) · Expert Opinion on Biological Therapy · doi:10.1517/14712590902828285 · Cited by 40
Wang, Z., Chang, L., Klein, W. L., Thatcher, G. R. J., & Venton, D. L. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm034224e · Cited by 37
Grundman, M., & Black, R. S. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.436 · Cited by 30
Yu, J., Bakhos, L., Chang, L., Holterman, M., Klein, W. L., & Venton, D. L. (2002) · Journal of Molecular Neuroscience · doi:10.1007/s12031-002-0010-x · Cited by 24
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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
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