Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms.
Open accessAbstract
Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer's disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to predict the oligomer concentration and size at physiological concentrations of Aβ and suggests the mechanisms by which the ratio of Aβ42 to Aβ40 can affect cell toxicity. An increased ratio of Aβ42 to Aβ40 raises the fraction of oligomers containing Aβ42, which can increase the hydrophobicity of the oligomers and thus promote deleterious binding to the cell membrane and increase neuronal damage. Our results suggest that co-oligomers are a common form of aggregate when Aβ isoforms are present in solution and may potentially play a significant role in Alzheimer's disease.
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
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?
The relationship between amyloid beta monomer concentration and aggregate concentration is nonlinear, so small changes in monomer can result in larger increases in the number of aggregates.
“it is also worth noting that the relationship between Aβ monomer concentration and aggregate concentration is nonlinear, so small changes in monomer can result in larger increases in the number of aggregates [44]”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Protein folding and misfolding
Dobson, C. M. (2003) · Nature · doi:10.1038/nature02261 · Cited by 4,791 · see citing works
Self-citationSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · see citing works
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,453 · see citing works
Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201750200 · Cited by 1,452 · see citing works
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271 · see citing works
Structural conversion of neurotoxic amyloid-β1–42 oligomers to fibrils
Ahmed, M., Davis, J., Aucoin, D., Sato, T., Ahuja, S., Aimoto, S., Elliott, J. I., Van Nostrand, W. E., & Smith, S. O. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1799 · Cited by 1,111 · see citing works
Goedert, M. (2015) · Science · doi:10.1126/science.1255555 · Cited by 977 · see citing works
Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein
Cremades, N., Cohen, S. I. A., Deas, E., Abramov, A. Y., Chen, A. Y., Orte, Á., Sandal, M., Clarke, R. W., Dunne, P., Aprile, F. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.037 · Cited by 901 · see citing works
Self-citationStructure–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
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · see citing works
Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease
Mehta, P. D., Pirttilä, T., Mehta, S. P., Sersen, E. A., Aisen, P. S., & Wisniewski, H. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.1.100 · Cited by 582 · see citing works
Take five—BACE and the γ‐secretase quartet conduct Alzheimer's amyloid β‐peptide generation
Haass, C. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600061 · Cited by 547 · see citing works
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
Meisl, G., Yang, X., Hellstrand, E., Frohm, B., Kirkegaard, J. B., Cohen, S. I. A., Dobson, C. M., Linse, S. S., & Knowles, T. P. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1401564111 · Cited by 503 · see citing works
Self-citationMetastability of Native Proteins and the Phenomenon of Amyloid Formation
Baldwin, A. J., Knowles, T. P. J., Tartaglia, G. G., Fitzpatrick, A. W. P., Devlin, G. L., Shammas, S. L., Waudby, C. A., Mossuto, M. F., Meehan, S., Gras, S. L., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2017703 · Cited by 428 · see citing works
Self-citationHellstrand, E., Boland, B., Walsh, D. M., & Linse, S. S. (2009) · ACS Chemical Neuroscience · doi:10.1021/cn900015v · Cited by 394 · see citing works
Aβ40 Inhibits Amyloid Deposition<i>In Vivo</i>
Kim, J., Onstead, L., Randle, S., Price, R., Smithson, L., Zwizinski, C., Dickson, D. W., Golde, T., & McGowan, E. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4849-06.2007 · Cited by 359 · see citing works
Oligomeric Intermediates in Amyloid Formation: Structure Determination and Mechanisms of Toxicity
Fändrich, M. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.01.006 · Cited by 339 · see citing works
PRESENILE DEMENTIA AND ALZHEIMER'S DISEASE IN MONGOLISM
Olson, M. I., & Shaw, C. (1969) · Brain · doi:10.1093/brain/92.1.147 · Cited by 290 · see citing works
The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β1−40 peptide
Narayan, P. S., Orte, Á., Clarke, R. W., Bolognesi, B., Hook, S., Ganzinger, K. A., Meehan, S., Wilson, M. R., Dobson, C. M., & Klenerman, D. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2191 · Cited by 282 · see citing works
Self-citationSurfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation.
Soreghan, B. A., Kosmoski, J. V., & Glabe, C. G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61939-3 · Cited by 267 · see citing works
Structural Basis for Increased Toxicity of Pathological Aβ42:Aβ40 Ratios in Alzheimer Disease
Pauwels, K., Williams, T. L., Morris, K. L., Jonckheere, W., Vandersteen, A., Kelly, G., Schymkowitz, J., Rousseau, F., Pastore, A., Serpell, L. C., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.264473 · Cited by 253 · see citing works
Lichtenthaler, S. F., Wang, R., Grimm, H. S., Uljon, S., Masters, C. L., & Beyreuther, K. T. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3053 · Cited by 231 · see citing works
Conformational Differences between Two Amyloid β Oligomers of Similar Size and Dissimilar Toxicity
Ladiwala, A. R. A., Litt, J., Kane, R. S., Aucoin, D., Smith, S. O., Ranjan, S., Davis, J., Nostrand, W. E. V., & Tessier, P. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.329763 · Cited by 223 · 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
Interaction between Aβ(1−42) and Aβ(1−40) in Alzheimer's β-Amyloid Fibril Formation in Vitro
Hasegawa, K., Yamaguchi, I., Omata, S., Gejyo, F., & Naiki, H. (1999) · Biochemistry · doi:10.1021/bi991161m · Cited by 217 · see citing works
Thermodynamics of Aβ(1−40) Amyloid Fibril Elongation
O’Nuallain, B., Shivaprasad, S., Kheterpal, I., & Wetzel, R. B. (2005) · Biochemistry · doi:10.1021/bi050927h · Cited by 215 · see citing works
Proteasomes Activate Aggresome Disassembly and Clearance by Producing Unanchored Ubiquitin Chains
Hao, R., Nanduri, P., Rao, Y., Panichelli, R. S., Ito, A., Yoshida, M., & Yao, T. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.016 · Cited by 193 · see citing works
Preparation of Amyloid β‐Protein for Structural and Functional Studies
Teplow, D. B. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(06)13002-5 · Cited by 187 · see citing works
Cukalevski, R., Yang, X., Meisl, G., Weininger, U., Bernfur, K., Frohm, B., Knowles, T. P. J., & Linse, S. S. (2015) · Chemical Science · doi:10.1039/c4sc02517b · Cited by 155 · see citing works
Self-citationAlanine Scanning Mutagenesis of Aβ(1-40) Amyloid Fibril Stability
Williams, A. D., Shivaprasad, S., & Wetzel, R. B. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.01.041 · Cited by 152 · see citing works
Evaluating Amyloid-β Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer’s Disease
Hölttä, M., Hansson, O., Andréasson, U., Hertze, J., Minthon, L., Nägga, K., Andreasen, N., Zetterberg, H., & Blennow, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066381 · Cited by 142 · see citing works
Amyloid β Protein: Aβ40 Inhibits Aβ42 Oligomerization
Murray, M. M., Bernstein, S. L., Nyugen, V., Condron, M. M., Teplow, D. B., & Bowers, M. T. (2009) · Journal of the American Chemical Society · doi:10.1021/ja8092604 · Cited by 128 · see citing works
Evidence of the Existence of Micelles in the Fibrillogenesis of β-Amyloid Peptide
Sabaté, R., & Estelrich, J. (2005) · The Journal of Physical Chemistry B · doi:10.1021/jp050716m · Cited by 125 · see citing works
Yang, T., O’Malley, T. T., Kanmert, D., Jerecı̀ć, J., Zieske, L. R., Zetterberg, H., Hyman, B. T., Walsh, D. M., & Selkoe, D. J. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0100-y · Cited by 115 · see citing works
Tosatto, L., Horrocks, M. H., Dear, A. J., Knowles, T. P. J., Serra, M. D., Cremades, N., Dobson, C. M., & Klenerman, D. (2015) · Scientific Reports · doi:10.1038/srep16696 · Cited by 110 · see citing works
Self-citationAβ40 and Aβ42 Amyloid Fibrils Exhibit Distinct Molecular Recycling Properties
Sánchez, L., Madurga, S., Pukala, T. L., Vilaseca, M., López‐Iglesias, C., Robinson, C. V., Giralt, E., & Carulla, N. (2011) · Journal of the American Chemical Society · doi:10.1021/ja1117123 · Cited by 107 · see citing works
Rare Individual Amyloid-β Oligomers Act on Astrocytes to Initiate Neuronal Damage
Narayan, P. S., Holmström, K. M., Kim, D.-H., Whitcomb, D. J., Wilson, M. R., George‐Hyslop, P. S., Wood, N. W., Dobson, C. M., Cho, K., Abramov, A. Y., et al. (2014) · Biochemistry · doi:10.1021/bi401606f · Cited by 104 · see citing works
Self-citationSpecific Compositions of Amyloid-β Peptides as the Determinant of Toxic β-Aggregation
Yoshiike, Y., Chui, D., Akagi, T., Tanaka, N., & Takashima, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212785200 · Cited by 102 · see citing works
Prions, prionoids and pathogenic proteins in Alzheimer disease
Ashe, K., & Aguzzi, A. (2013) · Prion · doi:10.4161/pri.23061 · Cited by 95 · see citing works
Brender, J., Krishnamoorthy, J., Sciacca, M. F. M., Vivekanandan, S., D’Urso, L., Chen, J., Rosa, C. L., & Ramamoorthy, A. (2015) · The Journal of Physical Chemistry B · doi:10.1021/jp511758w · Cited by 94 · see citing works
Horrocks, M. H., Tosatto, L., Dear, A. J., Garcia, G. A., Iljina, M., Cremades, N., Serra, M. D., Knowles, T. P. J., Dobson, C. M., & Klenerman, D. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b01811 · Cited by 91 · see citing works
Self-citationNarayan, P. S., Ganzinger, K. A., McColl, J. T., Weimann, L., Meehan, S., Qamar, S., Carver, J. A., Wilson, M. R., George‐Hyslop, P. S., Dobson, C. M., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja3103567 · Cited by 82 · see citing works
Self-citationComparison of Aβ levels in the brain of familial and sporadic Alzheimer's disease
Hellström‐Lindahl, E., Viitanen, M. H., & Marutle, A. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.03.007 · Cited by 75 · see citing works
Brännström, K., Öhman, A., Nilsson, L., Pihl, M., Sandblad, L., & Olofsson, A. (2014) · Journal of the American Chemical Society · doi:10.1021/ja503535m · Cited by 74 · see citing works
Ding, H., Wong, P. T., Lee, E. L., Gafni, A., & Steel, D. G. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.05.035 · Cited by 73 · see citing works
アミロイド前駆体蛋白質の貫通膜領域のフェニルアラニン‐走査突然変異誘発により確認されたアルツハイマー病γ‐セクレターゼの切断特異性の機序
Lichtenthaler, S. F., Wang, R., Grimm, H., Uljon, S., Masters, C. L., & Beyreuther, K. (1999) · Proceedings of the National Academy of Sciences · Cited by 65 · see citing works
Clinical, Neuropathologic, and Biochemical Profile of the Amyloid Precursor Protein I716F Mutation
Guardia‐Laguarta, C., Pera, M., Clarimón, J., Molinuevo, J. L., Sánchez‐Valle, R., Lladó, A., Coma, M., Gómez‐Isla, T., Blesa, R., Ferrer, I., et al. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181c6b84d · Cited by 63 · see citing works
Co‐incorporation of Aβ40 and Aβ42 to form mixed pre‐fibrillar aggregates
Frost, D., Gorman, P. M., Yip, C. M., & Chakrabartty, A. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03415.x · Cited by 59 · see citing works
Schauerte, J. A., Wong, P., Wisser, K. C., Ding, H., Steel, D. G., & Gafni, A. (2010) · Biochemistry · doi:10.1021/bi901444w · Cited by 52 · see citing works
Garcia, G. A., Cohen, S. I. A., Dobson, C. M., & Knowles, T. P. J. (2014) · Physical Review E · doi:10.1103/physreve.89.032712 · Cited by 51 · see citing works
Self-citationIntrinsic Determinants of Neurotoxic Aggregate Formation by the Amyloid β Peptide
Brorsson, A., Bolognesi, B., Tartaglia, G. G., Shammas, S. L., Favrin, G., Watson, I. E., Lomas, D. A., Chiti, F., Vendruscolo, M., Dobson, C. M., et al. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.12.4320 · Cited by 50 · see citing works
Self-citationJohnson, R. D., Schauerte, J. A., Wisser, K. C., Gafni, A., & Steel, D. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023970 · Cited by 47 · see citing works
Suárez‐Calvet, M., Belbin, O., Pera, M., Badiola, N., Magrané, J., Guardia‐Laguarta, C., Muñoz, L., Colom‐Cadena, M., Clarimón, J., & Lleó, A. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12466 · Cited by 41 · see citing works
Single-Molecule Imaging Reveals Aβ42:Aβ40 Ratio-Dependent Oligomer Growth on Neuronal Processes
Johnson, R. D., Schauerte, J. A., Chang, C.-C., Wisser, K. C., Althaus, J. C., Carruthers, C. J. L., Sutton, M. A., Steel, D. G., & Gafni, A. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2012.12.051 · Cited by 33 · see citing works
Single-molecule two-colour coincidence detection to probe biomolecular associations
Orte, Á., Clarke, R. W., & Klenerman, D. (2010) · Biochemical Society Transactions · doi:10.1042/bst0380914 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Oosawa F. & Asakura S. (Academic Press, New York, 1975).
Cited by
Sorted by citations
Tolar, M., Hey, J., Power, A., & Abushakra, S. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126355 · Cited by 246 · see citing works
Michaels, T. C. T., Šarić, A., Habchi, J., Chia, S., Meisl, G., Vendruscolo, M., Dobson, C. M., & Knowles, T. P. J. (2018) · Annual Review of Physical Chemistry · doi:10.1146/annurev-physchem-050317-021322 · Cited by 215 · see citing works
Self-citationMilardi, D., Gazit, E., Radford, S. E., Xu, Y., Gallardo, R. U., Caflisch, A., Westermark, G. T., Westermark, P., Rosa, C. L., & Ramamoorthy, A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00981 · Cited by 199 · see citing works
Critical aggregation concentration for the formation of early Amyloid-β (1–42) oligomers
Novo, M., Freire, S., & Al‐Soufi, W. (2018) · Scientific Reports · doi:10.1038/s41598-018-19961-3 · Cited by 174 · see citing works
Sciacca, M. F. M., Tempra, C., Scollo, F., Milardi, D., & Rosa, C. L. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.02.022 · Cited by 138 · see citing works
The role of biomolecular condensates in protein aggregation
Visser, B. S., Lipiński, W. P., & Spruijt, E. (2024) · Nature Reviews Chemistry · doi:10.1038/s41570-024-00635-w · Cited by 138 · see citing works
Visualizing and trapping transient oligomers in amyloid assembly pathways
Cawood, E. E., Karamanos, T., Wilson, A. J., & Radford, S. (2020) · Biophysical Chemistry · doi:10.1016/j.bpc.2020.106505 · Cited by 109 · see citing works
De, S., Whiten, D. R., Ruggeri, F. S., Hughes, C. D., Rodrigues, M., Sideris, D. I., Taylor, C. G., Aprile, F. A., Muyldermans, S., Knowles, T. P. J., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0777-4 · Cited by 96 · see citing works
Self-citationRajani, R. M., Ellingford, R., Hellmuth, M., Harris, S. S., Taso, O. S., Graykowski, D., Lam, F. K. W., Arber, C., Fertan, E., Danial, J. S. H., et al. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002727 · Cited by 57 · see citing works
“…[28,42,43]; it is also worth noting that the relationship between A β monomer concentration and aggregate concentration is nonlinear, so small changes in monomer can result in larger increases in the number of aggregates [44], although this does not rule out additional contributing factors.”
BackgroundSelf-citationAmyloid-β oligomerization monitored by single-molecule stepwise photobleaching
Dresser, L. G., Hunter, P., Yendybayeva, F., Payne-Dwyer, A. L., Howard, J. A. L., Evans, G. J., Leake, M. C., & Quinn, S. D. (2020) · Methods · doi:10.1016/j.ymeth.2020.06.007 · Cited by 55 · see citing works
Quantifying Co-Oligomer Formation by α-Synuclein
Iljina, M., Dear, A. J., Garcia, G. A., De, S., Tosatto, L., Flagmeier, P., Whiten, D. R., Michaels, T. C. T., Frenkel, D., Dobson, C. M., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b03575 · Cited by 48 · see citing works
Self-citationPeters, D. G., Pollack, A. N., Cheng, K. C., Sun, D., Saido, T. C., Haaf, M., Yang, Q. X., Connor, J. R., & Meadowcroft, M. D. (2018) · Metallomics · doi:10.1039/c8mt00004b · Cited by 43 · see citing works
Scollo, F., & Rosa, C. L. (2020) · Life · doi:10.3390/life10080144 · Cited by 43 · see citing works
Bode, D. C., Stanyon, H. F., Hirani, T., Baker, M. D., Nield, J., & Viles, J. H. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.01.008 · Cited by 37 · see citing works
The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer’s Disease
Ehtezazi, T., Rahman, K., Davies, R., & Leach, A. G. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-220071 · Cited by 35 · see citing works
Barritt, J. D., Younan, N. D., & Viles, J. H. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201704618 · Cited by 33 · see citing works
Symmetry-breaking transitions in the early steps of protein self-assembly
Rosa, C. L., Condorelli, M., Compagnini, G., Lolicato, F., Milardi, D., Do, T. N., Karttunen, M., Pannuzzo, M., Ramamoorthy, A., Fraternali, F., et al. (2020) · European Biophysics Journal · doi:10.1007/s00249-020-01424-1 · Cited by 33 · see citing works
Alzheimer’s Aβ42 and Aβ40 form mixed oligomers with direct molecular interactions
Gu, L., & Guo, Z. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.11.092 · Cited by 31 · see citing works
Stefaniak, E., Atrián‐Blasco, E., Goch, W., Sabater, L., Hureau, C., & Bal, W. (2020) · Chemistry - A European Journal · doi:10.1002/chem.202004484 · Cited by 26 · see citing works
De, S., & Klenerman, D. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2018.12.010 · Cited by 25 · see citing works
Self-citationMolecular Mechanism and Kinetics of Amyloid-β42 Aggregate Formation: A Simulation Study
Man, V. H., He, X., Ji, B., Liu, S., Xie, X., & Wang, J. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00473 · Cited by 26 · see citing works
Geerts, H., Walker, M., Rose, R., Bergeler, S., van der Graaf, P. H., Schuck, E. L., Koyama, A., Yasuda, S., Hussein, Z., Reyderman, L., et al. (2023) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12912 · Cited by 23 · see citing works
Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives
Wu, J., Cao, C., Loch, R. A., Tiiman, A., & Luo, J. (2020) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583520000086 · Cited by 23 · see citing works
Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology
Blömeke, L., Rehn, F., Kraemer‐Schulien, V., Kutzsche, J., Pils, M., Bujnicki, T., Lewczuk, P., Kornhuber, J., Freiesleben, S. D., Schneider, L., et al. (2024) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12589 · Cited by 22 · see citing works
Distinguishing the Effect on the Rate and Yield of Aβ42 Aggregation by Green Tea Polyphenol EGCG
Park, G., Xue, C., Wang, H., & Guo, Z. (2020) · ACS Omega · doi:10.1021/acsomega.0c02063 · Cited by 21 · see citing works
Kamynina, A. V., Esteras, N., Koroev, D. O., Бобкова, Н. В., Balasanyants, S. M., Simonyan, R. A., Avetisyan, A. V., Abramov, A. Y., & Volpina, O. M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00681 · Cited by 21 · see citing works
Weiffert, T., Meisl, G., Flagmeier, P., De, S., Dunning, C. J. R., Frohm, B., Zetterberg, H., Blennow, K., Portelius, E., Klenerman, D., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00676 · Cited by 20 · see citing works
Self-citationMeng, F., Kim, J.-Y., Louis, J. M., & Chung, H. S. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c06372 · Cited by 20 · see citing works
Lattanzi, V., Bernfur, K., Sparr, E., Olsson, U., & Linse, S. S. (2021) · JCIS Open · doi:10.1016/j.jciso.2021.100024 · Cited by 20 · see citing works
Ulku, I., Leung, R., Herre, F., Walther, L., Shobo, A., Säftig, P., Hancock, M. A., Liebsch, F., & Multhaup, G. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107510 · Cited by 20 · see citing works
Jeong, D., Kim, J., Chae, M.-S., Lee, W., Yang, S., Kim, Y. S., Kim, S. M., Lee, J. S., Lee, J. H., Choi, J., et al. (2018) · Sensors · doi:10.3390/s18061738 · Cited by 18 · see citing works
Honda, R. P. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201800197 · Cited by 17 · see citing works
Single Molecule Characterization of Amyloid Oligomers
Yang, J., Perrett, S., & Wu, S. (2021) · Molecules · doi:10.3390/molecules26040948 · Cited by 16 · see citing works
Shedding light on aberrant interactions – a review of modern tools for studying protein aggregates
Kundel, F., Tosatto, L., Whiten, D. R., Wirthensohn, D. C., Horrocks, M. H., & Klenerman, D. (2018) · FEBS Journal · doi:10.1111/febs.14409 · Cited by 15 · see citing works
Self-citationMeng, F., Kim, J.-Y., Gopich, I. V., & Chung, H. S. (2023) · PNAS Nexus · doi:10.1093/pnasnexus/pgad253 · Cited by 15 · see citing works
Heo, C. E., Choi, T. S., & Kim, H. I. (2018) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2018.02.002 · Cited by 15 · see citing works
Liang, R., Tian, Y., & Viles, J. H. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102071 · Cited by 15 · see citing works
On the reversibility of amyloid fibril formation
Pálmadóttir, T., Getachew, J., Ortigosa-Pascual, L., Axell, E., Wei, J., Olsson, U., Knowles, T. P. J., & Linse, S. S. (2025) · Biophysics Reviews · doi:10.1063/5.0236947 · Cited by 14 · see citing works
Self-citationBinary Structure of Amyloid Beta Oligomers Revealed by Dual Recognition Mapping
Yoon, J., Kim, Y., & Park, J. W. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b01316 · Cited by 13 · see citing works
A label-free high-throughput protein solubility assay and its application to Aβ40
Lindberg, M., Axell, E., Sparr, E., & Linse, S. S. (2024) · Biophysical Chemistry · doi:10.1016/j.bpc.2023.107165 · Cited by 11 · see citing works
Statistical Mechanics of Globular Oligomer Formation by Protein Molecules
Dear, A. J., Šarić, A., Michaels, T. C. T., Dobson, C. M., & Knowles, T. P. J. (2018) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.8b07805 · Cited by 10 · see citing works
Self-citationShobo, A., Röntgen, A., Hancock, M. A., & Multhaup, G. (2022) · FEBS Letters · doi:10.1002/1873-3468.14358 · Cited by 10 · see citing works
Malik, S., De, I., Singh, M. P., Galanakis, C. M., Alamri, A. S., & Yadav, J. K. (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.131486 · Cited by 10 · see citing works
The p3 peptides (Aβ17-40/42) rapidly form amyloid fibrils that cross-seed with full-length Aβ
Tian, Y., Torres‐Flores, A. P., Shang, Q., Zhang, H., Khursheed, A., Tahirbegi, I. B., Pallier, P. N., & Viles, J. H. (2025) · Nature Communications · doi:10.1038/s41467-025-57341-4 · Cited by 11 · see citing works
Characterizing the Oligomers Distribution along the Aggregation Pathway of Amyloid Aβ1‐40 by NMR
Pagano, K., Rosa, L. D., Tomaselli, S., Molinari, H., D’Andrea, L. D., & Ragona, L. (2024) · Chemistry - A European Journal · doi:10.1002/chem.202400594 · Cited by 7 · see citing works
Characterizing heterogeneity in amyloid formation processes
Chung, H. S. (2024) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2024.102951 · Cited by 8 · see citing works
Hassan, M., Shahzadi, S., Raza, H., Abbasi, M. A., Alashwal, H., Zaki, N., Moustafa, A. A., & Seo, S. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1543670 · Cited by 8 · see citing works
Barritt, J. D., Younan, N. D., & Viles, J. H. (2017) · Angewandte Chemie · doi:10.1002/ange.201704618 · Cited by 8 · see citing works
Sengupta, P., & Mukhopadhyay, D. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04735-6 · Cited by 6 · see citing works
Khalifa, J., Bourgault, S., & Gaudreault, R. (2023) · Current Alzheimer Research · doi:10.2174/0115672050277001231213073043 · Cited by 6 · see citing works
Electrolyte-Gated Organic Field-Effect Transistor for Monitoring Amyloid Aggregation
Ruiz‐Molina, S., Martínez‐Domingo, C., Ricci, S., Casalini, S., & Mas‐Torrent, M. (2024) · ACS Applied Electronic Materials · doi:10.1021/acsaelm.4c01673 · Cited by 5 · see citing works
Piano-stool metal complexes as inhibitors of amyloid-β aggregation in vitro and in vivo
Vigueras, G., Sabaté, R., Barrios, L. A., Caballero, A. B., Hernández‐García, S., Bayón, P., Gandía‐Herrero, F., Ruiz, J., & Gámez, P. (2024) · Inorganic Chemistry Frontiers · doi:10.1039/d4qi01460j · Cited by 4 · see citing works
Furlepa, M., Zhang, Y. P., Lobanova, E., Kahanawita, L., Vivacqua, G., Williams‐Gray, C. H., & Klenerman, D. (2024) · Brain Communications · doi:10.1093/braincomms/fcae178 · Cited by 4 · see citing works
Self-citationDefining the Neuropathological Aggresome across in Silico, in Vitro, and ex Vivo Experiments
Gomes, G.-N. W., & Levine, Z. A. (2021) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c09193 · Cited by 4 · see citing works
Honda, R. P. (2018) · Angewandte Chemie · doi:10.1002/ange.201800197 · Cited by 3 · see citing works
Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer’s Pathogenesis
Houfkova, A., & Schmidt, M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05786-z · Cited by 2 · see citing works
Jegamohan, S., Jafari, M., Lauzon, M.-A., van de Ven, T. G. M., Bourgault, S., & Gaudreault, R. (2026) · Next Materials · doi:10.1016/j.nxmate.2026.102062 · Cited by 2 · see citing works
Linalool acts as a chemical chaperone by inhibiting amyloid-β aggregation
Singh, R., Kaur, N., Dhingra, N., & Kaur, T. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105762 · Cited by 3 · see citing works
Multi-scale Assessment of Brain Blood Volume and Perfusion in the APP/PS1 Mouse Model of AmyloidosisPreprint
Munting, L. P., Derieppe, M., Voortman, L. M., Khmelinskii, A., Suidgeest, E., Hirschler, L., Barbier, E., de Senneville, B. D., & van der Weerd, L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.01.498298 · Cited by 2 · see citing works
Molecular mechanisms of amyloid aggregation in human proteinopathies
Morel, B., & Conejero‐Lara, F. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819132-3.00008-7 · Cited by 1 · see citing works
Amyloid-β aggregates induced by β-cholesteryl glucose-embedded liposomes.
Shimanouchi, T., Sano, Y., Yasuhara, K., & Kimura, Y. (2022) · Biochimica et Biophysica Acta - Proteins and Proteomics · doi:10.1016/j.bbapap.2022.140816 · Cited by 1 · see citing works
Amyloid beta: from pre-analytical factors to disease mechanisms
Toombs, J. (2019) · UCL Discovery (University College London)
Dear, A. J., Meisl, G., Axell, E., Yang, X., Cukalevski, R., Michaels, T. C. T., Linse, S. S., & Mahadevan, L. (2025) · Physical Chemistry Chemical Physics · doi:10.1039/d5cp01288k
Self-citationMan, V. H., He, X., Niu, T., Cai, L., Han, F., Nguyen, P. H., & Wang, J. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00003
Zherdova, N., Kopchak, O. O., Im, T., Perekhrestenko, O. V., Hrynevych, K., Stepura, O. A., & Orlyk, O. S. (2026) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.22.3.2026.1709
Targeting soluble misfolded oligomers in anti-amyloid research
Vosbein, P., Mao, H., & Lou, C. (2026) · Nature Reviews Chemistry · doi:10.1038/s41570-026-00867-y
Das, R., Biswas, S., & Mukhopadhyay, D. (2026) · Biochemistry · doi:10.1021/acs.biochem.6c00486
- Authors
- Iljina, M., Garcia, G. A., Dear, A. J., Flint, J., Narayan, P., Michaels, T. C. T., Dobson, C. M., Frenkel, D., Knowles, T. P. J., & Klenerman, D.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Knowles, Tuomas P. J.
- Klenerman, David
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-06-27
- Volume
- 6
- Issue
- 1
- Pages
- 28658-28658
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4921824
- OpenAlex
- W2473103627
- Cited by
- 68
- References
- 60
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 12 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 14 · 2017: 2
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Frances and Augustus Newman Foundation
- Schiff Foundation
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- amyloid-beta, Aβ40, amyloid-beta 42, co-oligomers, protein aggregation, Alzheimer's disease, single-molecule fluorescence, oligomer size distribution, cell membrane binding, neurotoxicity, isoform ratio
- MeSH terms
- Alzheimer Disease, Humans, Models, Chemical, Peptide Fragments, Amyloid beta-Peptides, Protein Isoforms, 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