Cited by 635Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis

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Viola, Kirsten L., Klein, William L.·2015·Acta Neuropathologica

DOI 10.1007/s00401-015-1386-3PMC PMC4390393

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Abstract

Protein aggregation is common to dozens of diseases including prionoses, diabetes, Parkinson's and Alzheimer's. Over the past 15 years, there has been a paradigm shift in understanding the structural basis for these proteinopathies. Precedent for this shift has come from investigation of soluble Aβ oligomers (AβOs), toxins now widely regarded as instigating neuron damage leading to Alzheimer's dementia. Toxic AβOs accumulate in AD brain and constitute long-lived alternatives to the disease-defining Aβ fibrils deposited in amyloid plaques. Key experiments using fibril-free AβO solutions demonstrated that while Aβ is essential for memory loss, the fibrillar Aβ in amyloid deposits is not the agent. The AD-like cellular pathologies induced by AβOs suggest their impact provides a unifying mechanism for AD pathogenesis, explaining why early stage disease is specific for memory and accounting for major facets of AD neuropathology. Alternative ideas for triggering mechanisms are being actively investigated. Some research favors insertion of AβOs into membrane, while other evidence supports ligand-like accumulation at particular synapses. Over a dozen candidate toxin receptors have been proposed. AβO binding triggers a redistribution of critical synaptic proteins and induces hyperactivity in metabotropic and ionotropic glutamate receptors. This leads to Ca(2+) overload and instigates major facets of AD neuropathology, including tau hyperphosphorylation, insulin resistance, oxidative stress, and synapse loss. Because different species of AβOs have been identified, a remaining question is which oligomer is the major pathogenic culprit. The possibility has been raised that more than one species plays a role. Despite some key unknowns, the clinical relevance of AβOs has been established, and new studies are beginning to point to co-morbidities such as diabetes and hypercholesterolemia as etiological factors. Because pathogenic AβOs appear early in the disease, they offer appealing targets for therapeutics and diagnostics. Promising therapeutic strategies include use of CNS insulin signaling enhancers to protect against the presence of toxins and elimination of the toxins through use of highly specific AβO antibodies. An AD-dependent accumulation of AβOs in CSF suggests their potential use as biomarkers and new AβO probes are opening the door to brain imaging. Overall, current evidence indicates that Aβ oligomers provide a substantive molecular basis for the cause, treatment and diagnosis of Alzheimer's disease.

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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
Retracted
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
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
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
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-citation
Journal of Biological Chemistry
Kurkinensp, M., CondongT, M. R., Blumberg, B., Barlow, D. P., Quiñones, S., Sausg, J., & Pihlajaniemisyy, T. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc · Cited by 3,427
Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo
Yang, 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
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes
Benilova, I., Karran, E., & De Strooper, B. (2012) · Nature Neuroscience · doi:10.1038/nn.3028 · Cited by 1,962
High-Level Neuronal Expression of Aβ1–42in Wild-Type Human Amyloid Protein Precursor Transgenic Mice: Synaptotoxicity without Plaque Formation
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856

Show all 198 references

Research works printed but not linked: 1

Nigh AB, Vahedi S, Davis EG, Weintraub S, Bigio EH, Klein WL, Geula C (2014) Intracellular Amyloid-beta in cholinergic neurons. Brain J Neurol: In Press

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Self-citation
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Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810
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Zott, B., Simon, M. M., Hong, W., Unger, F., Chen-Engerer, H.-J., Frosch, M. P., Sakmann, B., Walsh, D. M., & Konnerth, A. (2019) · Science · doi:10.1126/science.aay0198 · Cited by 640
Alzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689
“Because pathogenic soluble aggregates of Aβ appear early in the sequence of AD, they can represent interesting targets for therapeutics and diagnostics [51].”
Background
Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease
Söderberg, L., Johannesson, M., Nygren, P., Laudon, H., Eriksson, F., Osswald, G., Möller, C., & Lannfelt, L. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01308-6 · Cited by 459
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Karran, E., & De Strooper, B. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13632 · Cited by 402
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Ferreira, S. T., Lourenco, M. V., Oliveira, M. M., & De Felice, F. G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00191 · Cited by 373
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Sehar, U., Rawat, P., Reddy, A. P., Kopel, J. J., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112924 · Cited by 409
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the Synaptic Health Endpoints Working Group, Colom-Cadena, M., Spires-Jones, T., Zetterberg, H., Blennow, K., Caggiano, A., DeKosky, S. T., Fillit, H., Harrison, J. E., Schneider, L. S., et al. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00588-4 · Cited by 328
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Jeremic, D., Jiménez-Díaz, L., & Navarro-López, J. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101496 · Cited by 306
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Muralidar, S., Ambi, S. V., Sekaran, S., Thirumalai, D., & Palaniappan, B. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.327 · Cited by 278
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Zuroff, L. R., Daley, D. A., Black, K. L., & Koronyo‐Hamaoui, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2463-7 · Cited by 292
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Jarosz-Griffiths, H. H., Noble, E., Rushworth, J. V., & Hooper, N. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.702704 · Cited by 256
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Folch, J., Busquets, O., Ettcheto, M., Sánchez-López, E., Castro-Torres, R. D., Verdaguer, E., Garcia, M. L., Olloquequi, J., Casadesús, G., Beas-Zarate, C., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170672 · Cited by 245
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Tolar, M., Hey, J., Power, A., & Abushakra, S. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126355 · Cited by 253
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Saleem, S., & Kannan, R. R. (2018) · Cell Death Discovery · doi:10.1038/s41420-018-0109-7 · Cited by 241
Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer’s disease
Sehlin, D., Fang, X. T., Cato, L., Antoni, G., Lannfelt, L., & Syvänen, S. (2016) · Nature Communications · doi:10.1038/ncomms10759 · Cited by 226
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Ahmad, A., Ali, T., Park, H. Y., Badshah, H., Rehman, S. U., & Kim, M. O. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9795-4 · Cited by 216
Retracted
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Liu, Z., Li, T., Li, P., Wei, N., Zhao, Z., Liang, H., Ji, X., Chen, W., Xue, M., & Wei, J. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/352723 · Cited by 221
Challenges for Alzheimer's Disease Therapy: Insights from Novel Mechanisms Beyond Memory Defects
Frozza, R. L., Lourenco, M. V., & Felice, F. G. D. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00037 · Cited by 213
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Jones, M. R., Mathieu, É., Dyrager, C., Faissner, S., Vaillancourt, Z., Korshavn, K. J., Lim, M. H., Ramamoorthy, A., Yong, V. W., Tsutsui, S., et al. (2017) · Chemical Science · doi:10.1039/c7sc01269a · Cited by 96
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Xu, J., Gao, H. Y., Zhang, L., Rong, S., Yang, W. Q., Ma, C., Chen, M., Huang, Q., Deng, Q., & Huang, F. (2019) · Journal of Pineal Research · doi:10.1111/jpi.12584 · Cited by 93
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Seong, S. H., Ali, M. Y., Kim, H., Jung, H. A., & Choi, J. S. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.05.033 · Cited by 61

Authors: Viola, K. L., & Klein, W. L.
Affiliations: Northwestern University (US)
Corresponding author: Klein, William L.
ORCID: Viola, Kirsten L.
Klein, William L.
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2015-01-22
Volume: 129
Issue: 2
Pages: 183-206
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-015-1386-3
PMC: PMC4390393
OpenAlex: W2055775253
Cited by: 628
References: 198
Citations by year: 2026: 42 · 2025: 45 · 2024: 55 · 2023: 51 · 2022: 75 · 2021: 69 · 2020: 66 · 2019: 58 · 2018: 60 · 2017: 53 · 2016: 42 · 2015: 10
FWCI: 6.76
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (AG045637, AG029460, R01AG022547, AG022547, R01AG029460, R21AG045637)
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 oligomers, Alzheimer's disease pathogenesis, protein aggregation, neurotoxicity, synaptic dysfunction, glutamate receptors, calcium overload, tau hyperphosphorylation, insulin resistance, oxidative stress, synaptic loss, cerebrospinal fluid biomarkers, diabetes comorbidity, hypercholesterolemia, Alzheimer's disease therapeutics
MeSH terms: Alzheimer Disease, Animals, Humans, Neurons, Amyloid beta-Peptides

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Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis

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