The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

Benilova, Iryna; Karran, Eric; De Strooper, Bart

doi:10.1038/nn.3028

Cited by 1,962Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

Benilova, Iryna, Karran, Eric, De Strooper, Bart·2012·Nature Neuroscience

DOI 10.1038/nn.3028

Open this paper in CoChat — free account

Abstract

The 'toxic Aβ oligomer' hypothesis has attracted considerable attention among Alzheimer's disease researchers as a way of resolving the lack of correlation between deposited amyloid-β (Aβ) in amyloid plaques-in terms of both amount and location-and cognitive impairment or neurodegeneration. However, the lack of a common, agreed-upon experimental description of the toxic Aβ oligomer makes interpretation and direct comparison of data between different research groups impossible. Here we critically review the evidence supporting toxic Aβ oligomers as drivers of neurodegeneration and make some suggestions that might facilitate progress in this complex field.

Integrity signals

Registry

Crossref · 10.1038/nn.3028

Cites

102 of 102 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Longer Aβ peptides (≥Aβ42) are more prone to aggregation of toxic Aβ-species.
“It is widely accepted that longer Aβ peptides (≥Aβ42) are more prone to aggregation of toxic Aβ-species (43, 44).”
From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [44]
Aβ oligomers are the most neurotoxic Aβ species, driving synaptic dysfunction, neuronal loss and cognitive decline in AD.
“Evidence suggests that Aβ oligomers are the most neurotoxic Aβ species, driving synaptic dysfunction, neuronal loss and cognitive decline in AD [25–27].”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [25]
There is no direct clinical or preclinical in vivo evidence that disaggregating plaques releases damaging oligomeric amyloid-beta species.
“to our knowledge there is no direct clinical or preclinical in vivo evidence that this occurs”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [30]
Soluble oligomeric Aβ mediates synaptic dysfunction and neuronal toxicity.
“This was followed by evidence indicating that soluble oligomeric Aβ mediates synaptic dysfunction and neuronal toxicity [31–33].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [31]
Repeated failures of Aβ-targeting drugs have brought the amyloid hypothesis under fire.
“Yet, the repeated failures of these drugs have brought the amyloid hypothesis under fire [19, 31, 34].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [31]

2 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× · see citing works
“In Tg2576 transgenic mice that overexpress Swedish-mutated human APP, a 56-kDa species called Aβa56 was correlated with cognitive deficit”
Background
Retracted
RETRACTED: Cognitive effects of cell-derived and synthetically derived Aβ oligomers
Reed, M. N., Hofmeister, J. J., Jungbauer, L. M., Welzel, A. T., Yu, C., Sherman, M. A., Lesné, S., LaDu, M. J., Walsh, D. M., Ashe, K. H., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.11.007 · Cited by 132 · see citing works
Retracted
The 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 · see citing works
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 · see citing works
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 · see citing works
Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685 · see citing works
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 · see citing works
The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188 · see citing works
Self-citation
The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · see citing works
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821 · see citing works
Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils
Petkova, A. T., Leapman, R. D., Guo, Z., Yau, W.-M., Mattson, M. P., & Tycko, R. (2005) · Science · doi:10.1126/science.1105850 · Cited by 1,687 · see citing works
Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., & Ashe, K. H. (2004) · Nature Neuroscience · doi:10.1038/nn1372 · Cited by 1,677 · see citing works
P <scp>ROTOFIBRILS</scp> , P <scp>ORES</scp> , F <scp>IBRILS, AND</scp> N <scp>EURODEGENERATION</scp> : Separating the Responsible Protein Aggregates from The Innocent Bystanders
Caughey, B., & Lansbury, P. T. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.010302.081142 · Cited by 1,650 · see citing works
Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009) · Nature · doi:10.1038/nature07761 · Cited by 1,560 · see citing works
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,227 · cited 7× · see citing works
“Eisele, Y.S. et al. Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis.”
BackgroundInfluential
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation
Nilsberth, C., Westlind-Danielsson, A., Eckman, C. B., Condron, M. M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D. B., Younkin, S. G., et al. (2001) · Nature Neuroscience · doi:10.1038/nn0901-887 · Cited by 1,209 · see citing works
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Lomakin, A., Benedek, G. B., Condron, M. M., & Teplow, D. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.22364 · Cited by 1,139 · see citing works
A General Model of Prion Strains and Their Pathogenicity
Collinge, J., & Clarke, A. R. (2007) · Science · doi:10.1126/science.1138718 · Cited by 1,058 · see citing works
Calcium Dysregulation and Membrane Disruption as a Ubiquitous Neurotoxic Mechanism of Soluble Amyloid Oligomers*♦
Demuro, A., Mina, E. W., Kayed, R., Milton, S. C. F., Parker, I., & Glabe, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500997200 · Cited by 1,038 · see citing works
Soluble Oligomers of Amyloid β Protein Facilitate Hippocampal Long-Term Depression by Disrupting Neuronal Glutamate Uptake
Li, S., Hong, S., Shepardson, N. E., Walsh, D. M., Shankar, G. M., & Selkoe, D. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.012 · Cited by 972 · see citing works
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., et al. (2006) · Science · doi:10.1126/science.1131864 · Cited by 971 · see citing works
Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration
Jin, M., Shepardson, N., Yang, T., Chen, G., Walsh, D., & Selkoe, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017033108 · Cited by 876 · see citing works
In vitro aging of ß-amyloid protein causes peptide aggregation and neurotoxicity
Pike, C. J., Walencewicz, A. J., Glabe, C. G., & Cotman, C. W. (1991) · Brain Research · doi:10.1016/0006-8993(91)91553-d · Cited by 829 · see citing works
The amyloid hypothesis for Alzheimer’s disease: A critical reappraisal
Hardy, J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06181.x · Cited by 814 · see citing works
Structure–neurotoxicity relationships of amyloid β-protein oligomers
Ono, K., Condron, M. M., & Teplow, D. B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905127106 · Cited by 774 · see citing works
Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers
Kayed, R., Head, E., Sarsoza, F., Saing, T., Cotman, C. W., Necula, M., Margol, L., Wu, J., Breydo, L., Thompson, J. L., et al. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-18 · Cited by 773 · see citing works
Multimodal techniques for diagnosis and prognosis of Alzheimer's disease
Perrin, R. J., Fagan, A. M., & Holtzman, D. M. (2009) · Nature · doi:10.1038/nature08538 · Cited by 702 · see citing works
Observation of metastable Aβ amyloid protofibrils by atomic force microscopy
Harper, J. D., Wong, S. S., Lieber, C. M., & Lansbury, P. T. (1997) · Chemistry & Biology · doi:10.1016/s1074-5521(97)90255-6 · Cited by 691 · see citing works
Aβ Oligomers Cause Localized Ca 2+ Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines
Zempel, H., Thies, E., Mandelkow, E., & Mandelkow, E.-M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.2357-10.2010 · Cited by 686 · see citing works
Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers
Townsend, M., Shankar, G. M., Mehta, T., Walsh, D. M., & Selkoe, D. J. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2005.103754 · Cited by 619 · see citing works
What is the role of protein aggregation in neurodegeneration?
Ross, C. A., & Poirier, M. A. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1742 · Cited by 604 · see citing works
Peripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis
Eisele, Y. S., Obermüller, U., Heilbronner, G., Baumann, F., Kaeser, S. A., Wolburg, H., Walker, L. C., Staufenbiel, M., Heikenwalder, M., & Jucker, M. (2010) · Science · doi:10.1126/science.1194516 · Cited by 568 · see citing works
Globular amyloid β‐peptide 1−42 oligomer − a homogenous and stable neuropathological protein in Alzheimer's disease
Barghorn, S., Nimmrich, V., Striebinger, A., Krantz, C., Keller, P., Janson, B., Bahr, M., Schmidt, M., Bitner, R. S., Harlan, J., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03407.x · Cited by 559 · see citing works
A causative link between the structure of aberrant protein oligomers and their toxicity
Campioni, S., Mannini, B., Zampagni, M., Pensalfini, A., Parrini, C., Evangelisti, E., Relini, A., Stefani, M., Dobson, C. M., Cecchi, C., et al. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.283 · Cited by 552 · see citing works
Neurotoxicity of Alzheimer’s disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio
Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.211 · Cited by 532 · see citing works
Self-citation
Prions: Protein Aggregation and Infectious Diseases
Aguzzi, A., & Calella, A. M. (2009) · Physiological Reviews · doi:10.1152/physrev.00006.2009 · Cited by 502 · see citing works
Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β
Hoshi, M. M., Sato, M., Matsumoto, S., Noguchi, A., Yasutake, K., Yoshida, N., & Sato, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1237107100 · Cited by 494 · see citing works
Morphology and Toxicity of Aβ-(1-42) Dimer Derived from Neuritic and Vascular Amyloid Deposits of Alzheimer's Disease
Roher, A. E., Chaney, M. O., Kuo, Y., Webster, S. D., Stine, W. B., Haverkamp, L. J., Woods, A. S., Cotter, R. J., Tuohy, J. M., Krafft, G. A., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20631 · Cited by 494 · see citing works
Different Conformations of Amyloid β Induce Neurotoxicity by Distinct Mechanisms in Human Cortical Neurons
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 490 · see citing works
The presenilin hypothesis of Alzheimer’s disease: Evidence for a loss-of-function pathogenic mechanism.
Shen, J., & Kelleher, R. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608332104 · Cited by 485 · see citing works
β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In VitroandIn VivoMechanisms Related to Alzheimer's Disease
Dineley, K. T., Westerman, M., Bui, D., Bell, K., Ashe, K. H., & Sweatt, J. D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04125.2001 · Cited by 462 · see citing works
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
De Strooper, B. (2010) · Physiological Reviews · doi:10.1152/physrev.00023.2009 · Cited by 455 · see citing works
Self-citation
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 · see citing works
Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide
Hu, X., Crick, S. L., Bu, G., Frieden, C., Pappu, R. V., & Lee, J.-M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911281106 · Cited by 426 · see citing works
A new amyloid β variant favoring oligomerization in Alzheimer's‐type dementia
Tomiyama, T., Nagata, T., Shimada, H., Teraoka, R., Fukushima, A., Kanemitsu, H., Takuma, H., Kuwano, R., Imagawa, M., Ataka, S., et al. (2008) · Annals of Neurology · doi:10.1002/ana.21321 · Cited by 414 · see citing works
Amyloid-β forms fibrils by nucleated conformational conversion of oligomers
Lee, J., Culyba, E. K., Powers, E. T., & Kelly, J. W. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.624 · Cited by 383 · see citing works
Amyloid β Induces the Morphological Neurodegenerative Triad of Spine Loss, Dendritic Simplification, and Neuritic Dystrophies through Calcineurin Activation
Wu, H.-Y., Hudry, E., Hashimoto, T., Kuchibhotla, K., Rozkalne, A., Fan, Z., Spires-Jones, T., Xie, H., Arbel-Ornath, M., Grosskreutz, C. L., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4456-09.2010 · Cited by 367 · see citing works
Ion mobility–mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation
Bleiholder, C., Dupuis, N., Wyttenbach, T., & Bowers, M. T. (2010) · Nature Chemistry · doi:10.1038/nchem.945 · Cited by 367 · see citing works
Aggregation of Secreted Amyloid β-Protein into Sodium Dodecyl Sulfate-stable Oligomers in Cell Culture
Podlisny, M. B., Ostaszewski, B. L., Squazzo, S. L., Koo, E. H., Rydel, R. E., Teplow, D. B., & Selkoe, D. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9564 · Cited by 364 · see citing works
Stabilization of neurotoxic Alzheimer amyloid-β oligomers by protein engineering
Sandberg, A., Luheshi, L. M., Söllvander, S., Pereira de Barros, T., Macao, B., Knowles, T. P. J., Biverstål, H., Lendel, C., Ekholm-Petterson, F., Dubnovitsky, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001740107 · Cited by 358 · see citing works
Clusterin (apoJ) Alters the Aggregation of Amyloid β-Peptide (Aβ1-42) and Forms Slowly Sedimenting Aβ Complexes That Cause Oxidative Stress
Oda, T., Wals, P., Osterburg, H. H., Johnson, S. A., Pasinetti, G. M., Morgan, T. E., Rozovsky, I., Stine, W. B., Snyder, S. W., Holzman, T. F., et al. (1995) · Experimental Neurology · doi:10.1006/exnr.1995.1080 · Cited by 352 · see citing works
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 · see citing works
Conformational Abs recognizing a generic amyloid fibril epitope
O’Nuallain, B., & Wetzel, R. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022662599 · Cited by 331 · see citing works
Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation
Shipton, O. A., Leitz, J. R., Dworzak, J., Acton, C. E. J., Tunbridge, E. M., Denk, F., Dawson, H. N., Vitek, M. P., Wade-Martins, R., Paulsen, O., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2610-10.2011 · Cited by 315 · see citing works
Monoclonal 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 · see citing works
Aβ1-42 inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β
Jo, J., Whitcomb, D. J., Olsen, K. M., Kerrigan, T. L., Lo, S.-C., Bru-Mercier, G., Dickinson, B., Scullion, S., Sheng, M., Collingridge, G., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2785 · Cited by 305 · see citing works
Sensitive ELISA detection of amyloid‐β protofibrils in biological samples
Englund, H., Sehlin, D., Johansson, A., Nilsson, L. N. G., Gellerfors, P., Paulie, S., Lannfelt, L., & Pettersson, F. E. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04759.x · Cited by 292 · see citing works
Enhanced Production and Oligomerization of the 42-residue Amyloid β-Protein by Chinese Hamster Ovary Cells Stably Expressing Mutant Presenilins
Xia, W., Zhang, J., Kholodenko, D., Citron, M., Podlisny, M. B., Teplow, D. B., Haass, C., Seubert, P. A., Koo, E. H., & Selkoe, D. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.7977 · Cited by 282 · see citing works
Amyloid β-Protein Dimers Rapidly Form Stable Synaptotoxic Protofibrils
O'Nuallain, B., Freir, D. B., Nicoll, A. J., Risse, E., Ferguson, N., Herron, C. E., Collinge, J., & Walsh, D. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3537-10.2010 · Cited by 259 · see citing works
The Regulation of Glucose Metabolism by HIF-1 Mediates a Neuroprotective Response to Amyloid Beta Peptide
Soucek, T., Cumming, R., Dargusch, R., Maher, P., & Schubert, D. (2003) · Neuron · doi:10.1016/s0896-6273(03)00367-2 · Cited by 258 · see citing works
Targeting Amyloid-β Peptide (Aβ) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Aβ Precursor Protein (APP) Transgenic Mice
Lee, E. B., Leng, L. Z., Zhang, B., Kwong, L. K., Trojanowski, J. Q., Abel, T. G., & Lee, V. M. ‐. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511018200 · Cited by 252 · see citing works
The presence of sodium dodecyl sulphate-stable Aβ dimers is strongly associated with Alzheimer-type dementia
Donald, J. M. M., Savva, G. M., Brayne, C., Welzel, A. T., Forster, G., Shankar, G. M., Selkoe, D. J., Ince, P. G., & Walsh, D. M. (2010) · Brain · doi:10.1093/brain/awq065 · Cited by 251 · see citing works
Amyloid β‐protein monomer structure: A computational and experimental study
Baumketner, A., Bernstein, S. L., Wyttenbach, T., Bitan, G., Teplow, D. B., Bowers, M. T., & Shea, J. (2006) · Protein Science · doi:10.1110/ps.051762406 · Cited by 247 · see citing works
Nucleation-Dependent Polymerization Is an Essential Component of Amyloid-Mediated Neuronal Cell Death
Wogulis, M., Wright, S., Cunningham, D., Chilcote, T., Powell, K., & Rydel, R. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2381-04.2005 · Cited by 233 · see citing works
Pyroglutamate Formation Influences Solubility and Amyloidogenicity of Amyloid Peptides
Schlenzig, D., Manhart, S., Cinar, Y., Kleinschmidt, M., Hause, G., Willbold, D., Funke, S. A., Schilling, S., & Demuth, H.-U. (2009) · Biochemistry · doi:10.1021/bi900818a · Cited by 228 · see citing works
Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease
Schupf, N., Tang, M. X., Fukuyama, H., Manly, J., Andrews, H., Mehta, P., Ravetch, J., & Mayeux, R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805902105 · Cited by 225 · see citing works
Neurotoxic protein oligomers — what you see is not always what you get
Bitan, G., Fradinger, E. A., Spring, S. M., & Teplow, D. B. (2005) · Amyloid · doi:10.1080/13506120500106958 · Cited by 221 · see citing works
Extracellular phosphorylation of the amyloid β‐peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer's disease
Kumar, S., Rezaei‐Ghaleh, N., Terwel, D., Thal, D. R., Richard, M., Hoch, M., Donald, J. M. M., Wüllner, U., Glebov, K., Heneka, M. T., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.138 · Cited by 220 · see citing works
Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils
Habicht, G., Haupt, C., Friedrich, R. P., Hortschansky, P., Sachse, C., Meinhardt, J., Wieligmann, K., Gellermann, G. P., Brodhun, M., Götz, J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703793104 · Cited by 216 · see citing works
Adult-derived neural precursors transplanted into multiple regions in the adult brain
Herrera, D. G., García‐Verdugo, J. M., & Álvarez-Buylla, A. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199912)46:6 · Cited by 204 · see citing works
De novo induction of amyloid-β deposition in vivo
Morales, R., Duran-Aniotz, C. A., Castilla, J., Estrada, L. D., & Soto, C. A. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.120 · Cited by 190 · see citing works
Copper-mediated Amyloid-β Toxicity Is Associated with an Intermolecular Histidine Bridge
Smith, D. P., Smith, D. G., Curtain, C. C., Boas, J. F., Pilbrow, J. R., Ciccotosto, G. D., Lau, T., Tew, D. J., Perez, K. A., Wade, J. D., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600417200 · Cited by 186 · see citing works
Solution State Characterization of Amyloid β-Derived Diffusible Ligands
Hepler, R. W., Grimm, K. M., Nahas, D. D., Breese, R., Chen-Dodson, E., Acton, P. J., Keller, P. M., Yeager, M. D., Wang, H., Shughrue, P. J., et al. (2006) · Biochemistry · doi:10.1021/bi061850f · Cited by 184 · see citing works
Isolation and Characterization of Patient-derived, Toxic, High Mass Amyloid β-Protein (Aβ) Assembly from Alzheimer Disease Brains
Noguchi, A., Matsumura, S., Dezawa, M., Tada, M., Yanazawa, M., Ito, A., Akioka, M., Kikuchi, S., Sato, M., Ideno, S., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.000208 · Cited by 172 · see citing works
An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease
Lord, A., Gumucio, A., Englund, H., Sehlin, D., Sundquist, V. S., Söderberg, L., Möller, C., Gellerfors, P., Lannfelt, L., Pettersson, F. E., et al. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.08.007 · Cited by 157 · see citing works
Induction of β(A4)-amyloid in primates by injection of Alzheimer’s disease brain homogenate
Baker, H. F., Ridley, R. M., Duchen, L. W., Crow, T. J., & Bruton, C. J. (1994) · Molecular Neurobiology · doi:10.1007/bf02778005 · Cited by 149 · see citing works
Amyloid-β Annular Protofibrils Evade Fibrillar Fate in Alzheimer Disease Brain
Lasagna‐Reeves, C. A., Glabe, C. G., & Kayed, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.236257 · Cited by 136 · see citing works
NMDA receptor–dependent signaling pathways that underlie amyloid β‐protein disruption of LTP in the hippocampus
Yamin, G. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.21998 · Cited by 136 · see citing works
Amyloid-β-Derived Diffusible Ligands Cause Impaired Axonal Transport of Mitochondria in Neurons
Wang, X., Perry, G. L., Smith, M. A., & Zhu, X. (2010) · Neurodegenerative Diseases · doi:10.1159/000283484 · Cited by 126 · see citing works
Single-domain antibodies recognize selectively small oligomeric forms of amyloid β, prevent Aβ-induced neurotoxicity and inhibit fibril formation
Lafaye, P. J., Achour, I., England, P., Duyckaerts, C. J., & Rougeon, F. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.09.008 · Cited by 124 · see citing works
Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Aβ assembly forms throughout life
Shankar, G. M., Leissring, M. A., Adame, A., Sun, X., Spooner, E., Masliah, E., Selkoe, D. J., Lemere, C. A., & Walsh, D. M. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.021 · Cited by 123 · see citing works
Generation and Therapeutic Efficacy of Highly Oligomer-Specific β-Amyloid Antibodies
Hillen, H., Barghorn, S., Striebinger, A., Labkovsky, B., Müller, R., Nimmrich, V., Nolte, M. W., Perez-Cruz, C., van der Auwera, I., van Leuven, F., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5721-09.2010 · Cited by 113 · see citing works
Two Distinct Amyloid β-Protein (Aβ) Assembly Pathways Leading to Oligomers and Fibrils Identified by Combined Fluorescence Correlation Spectroscopy, Morphology, and Toxicity Analyses
Matsumura, S., Shinoda, K., Yamada, M., Yokojima, S., Inoue, M., Ohnishi, T., Shimada, T., Kikuchi, K., Masui, D., Hashimoto, S., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.181313 · Cited by 111 · see citing works
Molecular basis for passive immunotherapy of Alzheimer's disease
Gardberg, A. S., Dice, L. T., Ou, S. K.-H., Rich, R. L., Helmbrecht, E., Ko, J., Wetzel, R. B., Myszka, D. G., Patterson, P. H., & Dealwis, C. G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705888104 · Cited by 107 · see citing works
Transglutaminase Induces Protofibril-like Amyloid β-Protein Assemblies That Are Protease-resistant and Inhibit Long-term Potentiation
Hartley, D. M., Zhao, C., Speier, A. C., Woodard, G. A., Li, S., Li, Z., & Walz, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802215200 · Cited by 95 · see citing works
Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1A431E-associated familial Alzheimer's disease
Portelius, E., Andréasson, U., Ringman, J. M., Büerger, K., Daborg, J., Buchhave, P., Hansson, O., Harmsen, A., Gustavsson, M. K., Hanse, E., et al. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-2 · Cited by 94 · see citing works
High ability of apolipoprotein E4 to stabilize amyloid‐β peptide oligomers, the pathological entities responsible for Alzheimer's disease
Cerf, E., Gustot, A., Goormaghtigh, E., Ruysschaert, J., & Raussens, V. (2011) · The FASEB Journal · doi:10.1096/fj.10-175976 · Cited by 94 · see citing works
Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells
Zameer, A., Kasturirangan, S., Emadi, S., Nimmagadda, S. V., & Sierks, M. R. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.09.068 · Cited by 93 · see citing works
Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic β-Sheet Mimics
Liu, C., Sawaya, M. R., Cheng, P.-N., Zheng, J., Nowick, J. S., & Eisenberg, D. S. (2011) · Journal of the American Chemical Society · doi:10.1021/ja200222n · Cited by 92 · see citing works
The Monomer State of Beta-Amyloid: Where the Alzheimer's Disease Protein Meets Physiology
Giuffrida, M. L., Caraci, F., Bona, P. D., Pappalardo, G., Nicoletti, F., Rizzarelli, E., & Copani, A. (2010) · Reviews in the Neurosciences · doi:10.1515/revneuro.2010.21.2.83 · Cited by 91 · see citing works
In vitro peroxidase oxidation induces stable dimers of β-amyloid (1-42) through dityrosine bridge formation
Galeazzi, L., Ronchi, P., Franceschi, C., & Giunta, S. (1999) · Amyloid · doi:10.3109/13506129908993282 · Cited by 87 · see citing works
P4‐316: Stabilization of neurotoxic Alzheimer amyloid‐beta oligomers by protein engineering
Dubnovitsky, A. P., Sandberg, A., Luheshi, L. M., Söllvander, S., de Barros, T. P., Macao, B., Knowles, T. P. J., Biverstål, H., Lendel, C., Pettersson, F. E., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.09.061 · Cited by 80 · see citing works
Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease
Villemagne, V. L., Perez, K. A., Pike, K. E., Kok, W. M., Rowe, C. C., White, A. R., Bourgeat, P., Salvado, O., Bedő, J., Hutton, C. A., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5180-09.2010 · Cited by 71 · see citing works
Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide
Moretto, N., Bolchi, A., Rivetti, C., Imbimbo, B. P., Villetti, G., Pietrini, V., Polonelli, L., Signore, S. J. D., Smith, K. M., Ferrante, R. J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609690200 · Cited by 69 · see citing works
Erratum: De novo induction of amyloid-β deposition in vivo
Morales, R., Duran-Aniotz, C. A., Castilla, J., Estrada, L. D., & Soto, C. A. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.153 · Cited by 67 · see citing works
Direct in Vivo Intracellular Selection of Conformation-sensitive Antibody Domains Targeting Alzheimer's Amyloid-β Oligomers
Meli, G., Visintin, M., Cannistraci, I., & Cattaneo, A. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.01.061 · Cited by 61 · see citing works
G Protein–Coupled Receptors, Cholinergic Dysfunction, and Aβ Toxicity in Alzheimer’s Disease
Thathiah, A., & Strooper, B. D. (2009) · Science Signaling · doi:10.1126/scisignal.293re8 · Cited by 58 · see citing works
Anti-ADDL antibodies differentially block oligomer binding to hippocampal neurons
Shughrue, P. J., Acton, P. J., Breese, R., Zhao, W., Chen-Dodson, E., Hepler, R. W., Wolfe, A. L., Matthews, M., Heidecker, G. J., Joyce, J. G., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.04.003 · Cited by 53 · see citing works
Characterisation of two antibodies to oligomeric Aβ and their use in ELISAs on human brain tissue homogenates
Helmond, Z. V., Heesom, K. J., & Love, S. (2008) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.09.002 · Cited by 44 · see citing works
A monoclonal antibody against synthetic Aβ dimer assemblies neutralizes brain‐derived synaptic plasticity‐disrupting Aβ
O’Nuallain, B., Klyubin, I. V., Donald, J. M. M., Foster, J. S., Welzel, A. T., Barry, A. E., Dykoski, R. K., Cleary, J. P., Gebbink, M. F. B. G., Rowan, M. J., et al. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07389.x · Cited by 30 · see citing works
State of aggregation
(2011) · Nature Neuroscience · doi:10.1038/nn0411-399 · Cited by 25 · see citing works
Amyloid Goes Global
Bezprozvanny, I. B. (2009) · Science Signaling · doi:10.1126/scisignal.263pe16 · Cited by 19 · see citing works

Flagged first, then by citations

Sorted by citations

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
The Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990 · see citing works
Self-citation
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758 · see citing works
Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445 · see citing works
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases
Soto, C., & Pritzkow, S. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0235-9 · Cited by 1,180 · see citing works
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870 · see citing works
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · see citing works
Self-citation
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 · see citing works
RETRACTED ARTICLE: Pericyte loss influences Alzheimer-like neurodegeneration in mice
Sagare, A. P., Bell, R. D., Zhao, Z., Ma, Q., Winkler, E. A., Ramanathan, A., & Zlokovic, B. V. (2013) · Nature Communications · doi:10.1038/ncomms3932 · Cited by 589 · see citing works
Retracted
Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease
Morris, G. P., Clark, I. A., & Vissel, B. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0135-5 · Cited by 522 · see citing works
Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits
Xu, Z., Xiao, N., Chen, Y., Huang, H., Marshall, C., Gao, J., Cai, Z., Wu, T., Hu, G., & Xiao, M. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0056-1 · Cited by 500 · see citing works
Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
De, S., Wirthensohn, D. C., Flagmeier, P., Hughes, C., Aprile, F. A., Ruggeri, F. S., Whiten, D. R., Emin, D., Xia, Z., Varela, J. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09477-3 · Cited by 448 · see citing works
Biology and Genetics of Prions Causing Neurodegeneration
Prusiner, S. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155524 · Cited by 455 · see citing works
Amyloid toxicity in Alzheimer’s disease
Reiss, A. B., Arain, H. A., Stecker, M. M., Siegart, N. M., & Kasselman, L. J. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0063 · Cited by 447 · see citing works
Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology
Perez-Nievas, B. G., Stein, T. D., Tai, H.-C., Dols-Icardo, O., Scotton, T. C., Barroeta-Espar, I., Fernandez-Carballo, L., de Munain, E. L., Perez, J., Marquie, M., et al. (2013) · Brain · doi:10.1093/brain/awt171 · Cited by 387 · see citing works
Soluble amyloid-Î² oligomers as synaptotoxins leading to cognitive impairment in Alzheimerâ€™s disease
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 · see citing works
Meningeal Immunity and Its Function in Maintenance of the Central Nervous System in Health and Disease
Alves de Lima, K., Rustenhoven, J., & Kipnis, J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102319-103410 · Cited by 348 · see citing works
Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model
Wu, Z., Guo, Z., Gearing, M., & Chen, G. (2014) · Nature Communications · doi:10.1038/ncomms5159 · Cited by 306 · see citing works
Amyloid-beta peptide and tau protein crosstalk in Alzheimer’s disease
Villegas, S., Roda, A., Serra-Mir, G., Montoliu-Gaya, L., & Tiessler, L. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.332127 · Cited by 306 · see citing works
Amyloid β-protein oligomers and Alzheimer’s disease
Hayden, E. Y., & Teplow, D. B. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt226 · Cited by 276 · see citing works
Amyloid-β Receptors: The Good, the Bad, and the Prion Protein
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 · see citing works
Alzheimer’s-Causing Mutations Shift Aβ Length by Destabilizing γ-Secretase-Aβn Interactions
Szaruga, M., Munteanu, B., Lismont, S., Veugelen, S., Horré, K., Mercken, M., Saido, T. C., Ryan, N. S., De Vos, T., Savvides, S. N., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.004 · Cited by 248 · see citing works
Increased Microglial Exosomal miR-124-3p Alleviates Neurodegeneration and Improves Cognitive Outcome after rmTBI
Ge, X., Guo, M., Hu, T., Li, W., Huang, S., Yin, Z., Li, Y., Chen, F., Zhu, L., Kang, C., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.11.017 · Cited by 242 · see citing works
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease
Overk, C. R., & Masliah, E. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.015 · Cited by 242 · see citing works
Danger-associated molecular patterns in Alzheimer’s disease
Venegas, C., & Heneka, M. T. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0416-204r · Cited by 236 · see citing works
Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1449-5 · Cited by 235 · see citing works
Untangling Genetic Risk for Alzheimer’s Disease
Pimenova, A. A., Raj, T., & Goate, A. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.014 · Cited by 223 · see citing works
Effects of cannabidiol interactions with Wnt/&beta;-catenin pathway and PPAR&gamma; on oxidative stress and neuroinflammation in Alzheimer's disease
Vallée, A., Lecarpentier, Y., Guillevin, R., & Vallée, J.-N. (2017) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmx073 · Cited by 226 · see citing works
Dendritic Spine Pathology in Neurodegenerative Diseases
Herms, J., & Dorostkar, M. M. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044216 · Cited by 201 · see citing works
Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: a PET substudy interim analysis
Klein, G., Delmar, P., Voyle, N., Rehal, S., Hofmann, C., Abi-Saab, D., Andjelkovic, M., Ristic, S., Wang, G., Bateman, R., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0559-z · Cited by 212 · see citing works
Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease
Morris, G. P., Clark, I. A., & Vissel, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1918-8 · Cited by 212 · see citing works
Soluble Aβ Oligomers Are Rapidly Sequestered from Brain ISF In Vivo and Bind GM1 Ganglioside on Cellular Membranes
Hong, S., Ostaszewski, B. L., Yang, T., O’Malley, T. T., Jin, M., Yanagisawa, K., Li, S., Bartels, T., & Selkoe, D. J. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.027 · Cited by 213 · see citing works
Apolipoprotein E and Alzheimer's disease: the influence of apolipoprotein E on amyloid-β and other amyloidogenic proteins
Huynh, T.-P. V., Davis, A. A., Ulrich, J. D., & Holtzman, D. M. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075481 · Cited by 210 · see citing works
β-Amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1
Bourgade, K., Garneau, H., Giroux, G., Le Page, A. Y., Bocti, C., Dupuis, G., Frost, E. H., & Fülöp, T. (2015) · Biogerontology · doi:10.1007/s10522-014-9538-8 · Cited by 208 · see citing works
Friends or foes: matrix metalloproteinases and their multifaceted roles in neurodegenerative diseases
Brkic, M., Balusu, S., Libert, C., & Vandenbroucke, R. E. (2015) · Mediators of Inflammation · doi:10.1155/2015/620581 · Cited by 205 · see citing works
Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer’s disease immunotherapeutics
Goure, W. F., Krafft, G. A., Jerecic, J., & Hefti, F. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt272 · Cited by 190 · see citing works
Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease
Dionisio-Santos, D. A., Olschowka, J. A., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1453-0 · Cited by 184 · see citing works
APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons.
Moore, S., Evans, L. D. B., Andersson, T., Portelius, E., Smith, J., Dias, T. B., Saurat, N., McGlade, A., Kirwan, P., Blennow, K., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.068 · Cited by 179 · see citing works
Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease
Paula‐Lima, A. C., Brito‐Moreira, J., & Ferreira, S. T. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12304 · Cited by 170 · see citing works
N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits
Bouter, Y., Dietrich, K., Wittnam, J. L., Rezaei-Ghaleh, N., Pillot, T., Papot-Couturier, S., Lefebvre, T., Sprenger, F., Wirths, O., Zweckstetter, M., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1129-2 · Cited by 175 · see citing works
Imaging beta amyloid aggregation and iron accumulation in Alzheimer's disease using quantitative susceptibility mapping MRI
Gong, N.-J., Dibb, R., Bulk, M., van der Weerd, L., & Liu, C. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.02.019 · Cited by 162 · see citing works
Toll-like receptor 4-dependent glial cell activation mediates the impairment in memory establishment induced by β-amyloid oligomers in an acute mouse model of Alzheimer’s disease
Balducci, C., Frasca, A., Zotti, M., La Vitola, P., Mhillaj, E., Grigoli, E., Iacobellis, M., Grandi, F., Messa, M., Colombo, L., et al. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.10.012 · Cited by 164 · see citing works
A multi-pronged human microglia response to Alzheimer’s disease Aβ pathology
Mancuso, R., Fattorelli, N., Martinez-Muriana, A., Davis, E., Wolfs, L., Van Den Daele, J., Geric, I., Preman, P., Serneels, L., Poovathingal, S., et al. (2022) · doi:10.1101/2022.07.07.499139 · Cited by 169 · see citing works
Protective Effect of Amyloid-β Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model
Bourgade, K., Le Page, A., Bocti, C., Witkowski, J. M., Dupuis, G., Frost, E. H., & Fülöp, T. (2016) · Journal of Alzheimer’s Disease · doi:10.3233/jad-150652 · Cited by 161 · see citing works
Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis
Castellano, J. M., Deane, R., Gottesdiener, A. J., Verghese, P. B., Stewart, F. R., West, T., Paoletti, A. C., Kasper, T. R., DeMattos, R. B., Zlokovic, B. V., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206446109 · Cited by 154 · see citing works
APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses
Fogel, H., Frere, S., Segev, O., Bharill, S., Shapira, I., Gazit, N., O’Malley, T., Slomowitz, E., Berdichevsky, Y., Walsh, D. M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.024 · Cited by 138 · see citing works
Biochemically-defined pools of amyloid-β in sporadic Alzheimer’s disease: correlation with amyloid PET
Roberts, B. R., Lind, M., Wagen, A. Z., Rembach, A., Frugier, T., Li, Q.-X., Ryan, T. M., McLean, C. A., Doecke, J. D., Rowe, C. C., et al. (2017) · Brain · doi:10.1093/brain/awx057 · Cited by 143 · see citing works
Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models
Kostylev, M. A., Kaufman, A. C., Nygaard, H. B., Patel, P., Haas, L. T., Gunther, E. C., Vortmeyer, A., & Strittmatter, S. M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.643577 · Cited by 133 · see citing works
Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello, C., Yuan, P., & Grutzendler, J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.007 · Cited by 131 · see citing works
Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin
Ultsch, M., Li, B., Maurer, T., Mathieu, M., Adolfsson, O., Muhs, A., Pfeifer, A., Pihlgren, M., Bainbridge, T. W., Reichelt, M., et al. (2016) · Scientific Reports · doi:10.1038/srep39374 · Cited by 124 · see citing works
Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity
Nicoll, A. J., Panico, S., Freir, D. B., Wright, D., Terry, C., Risse, E., Herron, C. E., O’Malley, T., Wadsworth, J. D. F., Farrow, M. A., et al. (2013) · Nature Communications · doi:10.1038/ncomms3416 · Cited by 119 · see citing works
Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau
Rayaprolu, S., Higginbotham, L., Bagchi, P., Watson, C. M., Zhang, T., Levey, A. I., Rangaraju, S., & Seyfried, N. T. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-00840-3 · Cited by 118 · see citing works
Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
Sala Frigerio, C., & De Strooper, B. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014015 · Cited by 116 · see citing works
Accelerated microglial pathology is associated with <scp>A</scp> β plaques in mouse models of <scp>A</scp> lzheimer's disease
Baron, R., Babcock, A. A., Nemirovsky, A., Finsen, B., & Monsonego, A. (2014) · Aging Cell · doi:10.1111/acel.12210 · Cited by 118 · see citing works
Anti-Amyloid Therapies for Alzheimer’s Disease and the Amyloid Cascade Hypothesis
Fedele, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914499 · Cited by 102 · see citing works
Hippocampal Injections of Oligomeric Amyloid β-peptide (1–42) Induce Selective Working Memory Deficits and Long-lasting Alterations of ERK Signaling Pathway
Faucher, P., Mons, N., Micheau, J., Louis, C., & Beracochea, D. J. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00245 · Cited by 100 · see citing works
A glucan isolated from flowers of Lonicera japonica Thunb. inhibits aggregation and neurotoxicity of Aβ42
Wang, P., Liao, W., Fang, J., Liu, Q., Yao, J., Hu, M., & Ding, K. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2014.03.060 · Cited by 99 · see citing works
Cellular Receptors of Amyloid β Oligomers (AβOs) in Alzheimer’s Disease
Mroczko, B., Groblewska, M., Litman-Zawadzka, A., Kornhuber, J., & Lewczuk, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071884 · Cited by 97 · see citing works
Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a
Yang, Y., Kim, J., Kim, H. Y., Ryoo, N., Lee, S., Kim, Y., Rhim, H., & Shin, Y.-K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.044 · Cited by 88 · see citing works
Infectious origin of Alzheimer’s disease: Amyloid beta as a component of brain antimicrobial immunity
Vojtechova, I., Machacek, T., Kristofikova, Z., Stuchlik, A., & Petrasek, T. (2022) · PLOS Pathogens · doi:10.1371/journal.ppat.1010929 · Cited by 92 · see citing works
New Insights in Amyloid Beta Interactions with Human Telomerase
Wang, J., Zhao, C., Zhao, A., Li, M., Ren, J., & Qu, X. (2015) · Journal of the American Chemical Society · doi:10.1021/ja511030s · Cited by 90 · see citing works
Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer’s disease brains
Stern, A. M., Yang, Y., Jin, S., Yamashita, K., Meunier, A. L., Liu, W., Cai, Y., Ericsson, M., Liu, L., Goedert, M., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.04.007 · Cited by 91 · see citing works
Sensitive imaging and effective capture of Cu2+: Towards highly efficient theranostics of Alzheimer's disease
Cui, Z., Bu, W., Fan, W., Zhang, J., Ni, D., Liu, Y., Wang, J., Liu, J., Yao, Z., & Shi, J. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.06.056 · Cited by 83 · see citing works
Synaptic deficits in layer 5 neurons precede overt structural decay in 5xFAD mice
Buskila, Y., Crowe, S. E., & Ellis-Davies, G. C. R. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.09.016 · Cited by 77 · see citing works
Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models
Wirths, O., & Zampar, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218144 · Cited by 75 · see citing works
“While fibrillar Aβ species have been considered to be the main neurotoxic species in former times, more recent studies suggest that pre-fibrillar small soluble oligomeric Aβ variants are at least equally toxic [87,88].”
Background
Peripheral Administration of a Humanized Anti-PrP Antibody Blocks Alzheimer's Disease Aβ Synaptotoxicity
Klyubin, I., Nicoll, A. J., Khalili-Shirazi, A., Farmer, M., Canning, S., Mably, A., Linehan, J., Brown, A., Wakeling, M., Brandner, S., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3526-13.2014 · Cited by 74 · see citing works
Emerging β-amyloid pathology and accelerated cortical atrophy
Mattsson, N., Insel, P. S., Nosheny, R., Tosun, D., Trojanowski, J. Q., Shaw, L. M., Jack, C. R., Donohue, M. C., & Weiner, M. W. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.446 · Cited by 71 · see citing works
Modeling the complex pathology of Alzheimer's disease in Drosophila
Fernandez-Funez, P., de Mena, L., & Rincon-Limas, D. E. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.05.013 · Cited by 69 · see citing works
Promiscuous Alzheimer's Amyloid: Yet Another Partner
Benilova, I., & De Strooper, B. (2013) · Science · doi:10.1126/science.1244166 · Cited by 67 · see citing works
Self-citation
PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease
Giralt, A., de Pins, B., Cifuentes-Díaz, C., López-Molina, L., Farah, A. T., Tible, M., Deramecourt, V., Arold, S. T., Ginés, S., Hugon, J., et al. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.05.020 · Cited by 64 · see citing works
A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer’s disease
Sepulveda-Falla, D., Chavez-Gutierrez, L., Portelius, E., Vélez, J. I., Dujardin, S., Barrera-Ocampo, A., Dinkel, F., Hagel, C., Puig, B., Mastronardi, C., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-020-02249-0 · Cited by 54 · see citing works
N-truncated Abeta starting with position four: Early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody
Antonios, G., Saiepour, N., Bouter, Y., Richard, B. C., Paetau, A., Verkkoniemi-Ahola, A., Lannfelt, L., Ingelsson, M., Kovacs, G. G., Pillot, T., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-56 · Cited by 53 · see citing works
β-amyloid: The known unknowns
Ayton, S., & Bush, A. I. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101212 · Cited by 45 · see citing works
Characterization of the selective in vitro and in vivo binding properties of crenezumab to oligomeric Aβ
Meilandt, W. J., Maloney, J. A., Imperio, J., Lalehzadeh, G., Earr, T., Crowell, S., Bainbridge, T. W., Lu, Y., Ernst, J. A., Fuji, R. N., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0553-5 · Cited by 45 · see citing works
Amyloid-beta peptide decreases expression and function of glutamate transporters in nervous system cells
Tong, H., Zhang, X., Meng, X., Xu, P., Zou, X., & Qu, S. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.01.017 · Cited by 42 · see citing works
GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein
Nakamura, M., Li, Y., Choi, B.-R., Matas-Rico, E., Troncoso, J., Takahashi, C., & Sockanathan, S. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe6178 · Cited by 38 · see citing works
Three structural features of functional food components and herbal medicine with amyloid β42 anti-aggregation properties
Murakami, K., & Irie, K. (2019) · Molecules · doi:10.3390/molecules24112125 · Cited by 31 · see citing works
“Metastable oligomers of Aβ42 cause memory loss and synaptotoxicity, whereas the contribution of end-stage matured fibrils to the etiology of AD is smaller [7,8].”
Background
The absence of myelin basic protein promotes neuroinflammation and reduces amyloid β-protein accumulation in Tg-5xFAD mice
Ou-Yang, M.-H., & Van Nostrand, W. E. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-134 · Cited by 30 · see citing works
p47phox deficiency improves cognitive impairment and attenuates tau hyperphosphorylation in mouse models of AD
Gong, P., Chen, Y.-Q., Lin, A.-H., Zhang, H.-B., Zhang, Y., Ye, R. D., & Yu, Y. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00714-2 · Cited by 29 · see citing works
Real-Time Analysis of Binding Events between Different Aβ1–42 Species and Human Lilrb2 by Dual Polarization Interferometry
Hu, T., Wang, S., Chen, C., Sun, J., & Yang, X. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.6b04950 · Cited by 28 · see citing works
Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease
Fernández Zapata, C., Giacomello, G., Spruth, E. J., Middeldorp, J., Gallaccio, G., Dehlinger, A., Dames, C., Leman, J. K. H., van Dijk, R. E., Meisel, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34719-2 · Cited by 27 · see citing works
Antibody Engineering for Optimized Immunotherapy in Alzheimer's Disease
Sumner, I. L., Edwards, R. A., Asuni, A. A., & Teeling, J. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00254 · Cited by 24 · see citing works
The Chemerin/CMKLR1 Axis Is Involved in the Recruitment of Microglia to Aβ Deposition through p38 MAPK Pathway
Chen, Y., Liu, Z., Gong, P., Zhang, H., Chen, Y., Yao, S., Li, W., Zhang, Y., & Yu, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169041 · Cited by 25 · see citing works
Restoring microglial and astroglial homeostasis using DNA immunization in a down Syndrome mouse model.
Illouz, T., Madar, R., Biragyn, A., & Okun, E. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.10.004 · Cited by 22 · see citing works
Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression
Jendresen, C., Digre, A., Cui, H., Zhang, X., Vlodavsky, I., Li, J.-P., & Nilsson, L. N. G. (2019) · Scientific Reports · doi:10.1038/s41598-019-40999-4 · Cited by 19 · see citing works
Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice
Raulin, A.-C., Alnobani, A., Rodriguez-Martinez, P., Lee, E., Linares, C., Yslas, A. R., Li, M., Ren, Y., Doss, S. V., Roy, B., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04002-9

Covalent organic framework-based ratiometric electrochemical sensing platform for ultrasensitive determination of amyloid-β 42 oligomer
Liu, J., Zhao, H., Hu, S., Li, N., Cui, M., Han, B., Li, M., & Zhang, C. (2024) · Talanta · doi:10.1016/j.talanta.2024.126699 · Cited by 15 · see citing works
Oligomer Formation of Amyloid-β(29–42) from Its Monomers Using the Hamiltonian Replica-Permutation Molecular Dynamics Simulation
Itoh, S., & Okumura, H. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b03828 · Cited by 50 · see citing works
基礎の部 ● 演題 2デスミン心筋症マウスに対するニコランジルの心筋保護効果
三部篤 (2011) · Therapeutic research
P1‐451: The oligomerization of amyloid‐β peptide
Stone, L. A., Frykman, S., Winblad, B. G., et al. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.1034
Views on Amyloid Hypothesis and Secretase Inhibitors for Treating Alzheimers Disease: Progress and Problems
Nguyen, J., Yamani, A., & Kiso, Y. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206778792976 · Cited by 36 · see citing works

Authors: Benilova, I., Karran, E., & De Strooper, B.
Affiliations: KU Leuven (BE)
ORCID: Benilova, Iryna
Karran, Eric
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2012-01-29
Volume: 15
Issue: 3
Pages: 349-357
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.3028
OpenAlex: W2080225612
Cited by: 1,962
References: 102
Citations by year: 2026: 97 · 2025: 85 · 2024: 116 · 2023: 125 · 2022: 116 · 2021: 144 · 2020: 193 · 2019: 146 · 2018: 162 · 2017: 143 · 2016: 153 · 2015: 164 · 2014: 146 · 2013: 111 · 2012: 57
FWCI: 16.74
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Lirias (KU Leuven) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology › 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, Alzheimer's disease, amyloid plaques, neurodegeneration, cognitive impairment, amyloid-beta oligomers, amyloid-beta toxicity
MeSH terms: Alzheimer Disease, Animals, Cognition Disorders, Humans, Models, Biological, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurodegenerative Diseases, Mice

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

The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks