The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index.
Neurotoxicity of Alzheimer’s disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio
Open accessAbstract
The amyloid peptides Aβ(40) and Aβ(42) of Alzheimer's disease are thought to contribute differentially to the disease process. Although Aβ(42) seems more pathogenic than Aβ(40), the reason for this is not well understood. We show here that small alterations in the Aβ(42):Aβ(40) ratio dramatically affect the biophysical and biological properties of the Aβ mixtures reflected in their aggregation kinetics, the morphology of the resulting amyloid fibrils and synaptic function tested in vitro and in vivo. A minor increase in the Aβ(42):Aβ(40) ratio stabilizes toxic oligomeric species with intermediate conformations. The initial toxic impact of these Aβ species is synaptic in nature, but this can spread into the cells leading to neuronal cell death. The fact that the relative ratio of Aβ peptides is more crucial than the absolute amounts of peptides for the induction of neurotoxic conformations has important implications for anti-amyloid therapy. Our work also suggests the dynamic nature of the equilibrium between toxic and non-toxic intermediates.
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“The increased Aβ 42:40 ratio in oligodendrocytes could contribute to the high proportion of soluble aggregates [28,42,43]”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [43]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Aβ40 is present in larger amounts in the brain, yet Aβ42 is more neurotoxic and has a higher tendency to aggregate.8–11”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the longer and more hydrophobic Aβ42 isoform has a higher tendency to generate neurotoxic oligomeric species.9,10”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [10]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although Aβ40 is present in larger amounts in the brain, Aβ42 was found to be more neurotoxic and have a higher tendency to aggregate.4,5”
From The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity (2013) · cites this paper as [5]
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In the citing paper
“Although it was shown in previous studies9,10,21 that the Aβ42 peptide is more prone to form neurotoxic soluble Aβ oligomers than the Aβ40 peptide”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [10]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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“…potently disrupt synaptic plasticity (Klyubin et al, 2008; Shankar et al, 2008), an Ab species of 56 kDa has been found neurotoxic in Tg2576 mice (Lesne et al, 2006), lipid-induced oligomers from mature fibrils (Martins et al, 2008), ADDLs (Lambert et al, 1998; Gong et al, 2003; Lacor et al,…”
BackgroundRetractedThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
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Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
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Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
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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 1,722
Flagged first, then by citations
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Items 501–538 of 538
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612336
Motta, C., Donna, M. G. D., Bonomi, C. G., Assogna, M., Chiaravalloti, A., Mercuri, N. B., Koch, G., & Martorana, A. (2024) · Figshare · doi:10.6084/m9.figshare.26613760
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612333
Motta, C., Donna, M. G. D., Bonomi, C. G., Assogna, M., Chiaravalloti, A., Mercuri, N. B., Koch, G., & Martorana, A. (2024) · Figshare · doi:10.6084/m9.figshare.26613757
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612327
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612324
Motta, C., Donna, M. G. D., Bonomi, C. G., Assogna, M., Chiaravalloti, A., Mercuri, N. B., Koch, G., & Martorana, A. (2024) · Figshare · doi:10.6084/m9.figshare.26613754
Motta, C., Donna, M. G. D., Bonomi, C. G., Assogna, M., Chiaravalloti, A., Mercuri, N. B., Koch, G., & Martorana, A. (2024) · Figshare · doi:10.6084/m9.figshare.26613763
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612348
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612330
Hector, A., Provost, C., Delignat‐Lavaud, B., Bouamira, K., Menaouar, C.-A., Mongrain, V., & Brouillette, J. (2023) · Figshare · doi:10.6084/m9.figshare.24309863
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612345
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612342
Motta, C., Donna, M. G. D., Bonomi, C. G., Assogna, M., Chiaravalloti, A., Mercuri, N. B., Koch, G., & Martorana, A. (2024) · Figshare · doi:10.6084/m9.figshare.26613751
Sandberg, A., Berenjeno-Correa, E., Rodriguez, R. C., Axenhus, M., Weiss, S. S., Batenburg, K. L., Hoozemans, J. J. M., Tjernberg, L. O., & Scheper, W. (2023) · Figshare · doi:10.6084/m9.figshare.22612339
Li, X., Zhang, Y., Shi, X., Li, D., Yang, W., & Ma, A. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261418314
Yang, L., Song, G., Parker, E., & Yang, L. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05832-w
Molecular mechanisms of action of MT-MMPs involved in the pathogenesis of Alzheimer’s disease
García‐González, L. (2020) · theses.fr (ABES) · doi:10.70675/a04672c0z1f4az472ezbcd5zbea446eac50c
Valverde, A. (2020) · theses.fr (ABES) · doi:10.70675/f1b70734zf4e3z4870z8fbdz950d831642a7
Structural Basis of Frizzled-Wnt in Recognition of Aβ Unveils Mechanism of Aβ-Mediated Disruption
Mei, J., Zha, R., Qiu, Y., Du, Z., Liang, S., Sheng, L., & Hou, Y. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c01028
Sun, Q., Yin, X., Lang, Y., Zhang, B., Shao, J., Zhang, Y., Wang, Y., Wang, Y., & Cui, L. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e00957
Fukuchi, K.-I., Yang, J., & Williams, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1959643
Brain multiomic profiling identifies tau-related transcriptomic dysregulation in Alzheimer’s disease
Oatman, S. R., Quicksall, Z., Wang, X., Bergman, J., Reddy, J. S., Vanelderen, F., Nguyen, T., Malphrus, K. G., Lincoln, S., Martens, Y. A., et al. (2026) · Brain Communications · doi:10.1093/braincomms/fcag326
鉄処理がγセクレターゼを調節しAβ42/Aβ40比を下げることによって、 in vivoでのAβ42の沈着を抑制する
沈, 雪. (n.d.) · Institutional Repositories DataBase (IRDB)
ApoE4 impairs astrocyte lipid droplet formation via endolysosomal dysfunction
Ralhan, I., Bae, J.-Y., Lee, N. Y., Cai, W., Chang, J., Jarad, S., Gu, H., Zhang, D., & Ioannou, M. S. (2026) · doi:10.64898/2026.09.01.748585
BindingDB (2020) · UC San Diego · doi:10.7270/q2r78htv
BindingDB (2022) · UC San Diego · doi:10.7270/q2v69p6t
BindingDB Entry 50010006: Gamma Secretase Modulators: New Alzheimer's Drugs on the Horizon?
BindingDB (2021) · UC San Diego · doi:10.7270/q2b56p74
Metadata
- Authors
- Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., Braeken, D., Callewaert, G., Bartic, C., D'Hooge, R., Martins, I. C., Rousseau, F., Schymkowitz, J., & De Strooper, B.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- Vrije Universiteit Brussel (BE)
- Rega Institute for Medical Research (BE)
- University of Twente (NL)
- IMEC (BE)
- Corresponding author
- Schymkowitz, Joost
- ORCID
- Venue
- The EMBO Journal
- Published
- 2010-09-03
- Volume
- 29
- Issue
- 19
- Pages
- 3408-3420
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2957213
- OpenAlex
- W1966694507
- Cited by
- 532
- References
- 61
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 36 · 2023: 39 · 2022: 27 · 2021: 39 · 2020: 32 · 2019: 33 · 2018: 31 · 2017: 35 · 2016: 48 · 2015: 31 · 2014: 30 · 2013: 42 · 2012: 43
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion)
- University of Twente Research Information (publishedVersion, other-oa)
- Lirias (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- University of Twente Research Information (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- European Commission (200611)
- Fonds Wetenschappelijk Onderzoek (P6/43)
- Vlaamse regering
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, Aβ42/Aβ40 ratio, neurotoxicity, oligomeric intermediates, fibril morphology, synaptic dysfunction, neuronal cell death, anti-amyloid therapy, peptide mixtures
- MeSH terms
- Alzheimer Disease, Analysis of Variance, Animals, Biophysics, Fluorescent Dyes, Humans, Kinetics, Microelectrodes, Neurons, Peptide Fragments, Protein Binding, Thiazoles, Amyloid beta-Peptides, Spectroscopy, Fourier Transform Infrared, Patch-Clamp Techniques, Microscopy, Electron, Transmission, Mice, Benzothiazoles, Plaque, Amyloid
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