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Cited by 61Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Alzheimer therapy with an antibody against N-terminal Abeta 4-X and pyroglutamate Abeta 3-X

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Antonios, Gregory, Borgers, Henning, Richard, Bernhard C., Brauß, Andreas, Meißner, Julius, Weggen, Sascha, Pena, Vladimir, Pillot, Thierry +6 more·2015·Scientific Reports
DOI 10.1038/srep17338PMC PMC4667289
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Abstract

Full-length Aβ1-42 and Aβ1-40, N-truncated pyroglutamate Aβ3-42 and Aβ4-42 are major variants in the Alzheimer brain. Aβ4-42 has not been considered as a therapeutic target yet. We demonstrate that the antibody NT4X and its Fab fragment reacting with both the free N-terminus of Aβ4-x and pyroglutamate Aβ3-X mitigated neuron loss in Tg4-42 mice expressing Aβ4-42 and completely rescued spatial reference memory deficits after passive immunization. NT4X and its Fab fragment also rescued working memory deficits in wild type mice induced by intraventricular injection of Aβ4-42. NT4X reduced pyroglutamate Aβ3-x, Aβx-40 and Thioflavin-S positive plaque load after passive immunization of 5XFAD mice. Aβ1-x and Aβx-42 plaque deposits were unchanged. Importantly, for the first time, we demonstrate that passive immunization using the antibody NT4X is therapeutically beneficial in Alzheimer mouse models showing that N-truncated Aβ starting with position four in addition to pyroglutamate Aβ3-x is a relevant target to fight Alzheimer’s disease.

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  • Homozygous Tg4-42 mice display age-dependent neuron loss in the CA1 region of the hippocampus, reaching a plateau after 6 months of age, a time point when deficits become evident in a variety of behavioral tasks.

    “Homozygous Tg4–42 mice display an age-dependent neuron loss in the CA1 region of the hippocampus, reaching a plateau after 6 months of age, a time point when deficits become evident in a variety of behavioral tasks [27].”

    From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [27]

    The Results section on CA1 neuron loss reports age-dependent loss in homozygous Tg4-42 mice, but it rises from 50% at six months to 64% at eight months, contrary to a plateau after six months. The Results section on spatial reference memory reports clear deficits by six months in the Morris water maze, but does not establish deficits across a variety of behavioral tasks. Page numbers are unavailable in our copy. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • The lack of a difference in neuron numbers at 5 months might be attributed to the fact that single Tg4-42hom mice already show a profound CA1 neuron loss, reaching a kind of plateau at that time point.

    “The lack of such a difference in 5-month-old mice might be attributed to the fact that single Tg4–42hom mice already show a profound CA1 neuron loss, reaching a kind of plateau at that time point [27].”

    From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [27]

    The Results section reports substantial CA1 neuron loss in Tg4-42hom mice at five months (43%). It does not establish that this loss explains the citing paper’s lack of a difference between groups, and it reports further loss at six, seven, and eight months rather than a plateau at five months. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Tg4-42hom mice presented expected age-dependent neuron loss with total CA1 neuron loss of approximately 20%, 40% and 45% compared to WT mice at 3, 5 and 9 months, respectively.

    “Tg4–42hom mice presented the expected age-dependent neuron loss with a total CA1 (calculated as distal + proximal) neuron loss of approximately 20%, 40% and 45% compared to WT mice at 3, 5 and 9 months, respectively (Supplementary Figure S6), confirming previous data obtained with stereological analyses [27].”

    From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [27]

  • At 5 months, bigenic mice showed spatial memory deficits in the MWM task, however neuron numbers did not differ significantly from single transgenic Tg4-42hom mice still learning the task, confirming results from a previous study employing 5-month-old Tg4-42hom mice.

    “At this time point, bigenic mice showed spatial memory deficits in the MWM task, however, it has to be noted that neuron numbers did not differ significantly from single transgenic Tg4–42hom mice still learning the task, confirming results from a previous study employing 5-month-old Tg4–42hom mice [27].”

    From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [27]

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Authors
Antonios, G., Borgers, H., Richard, B. C., Brauß, A., Meißner, J., Weggen, S., Pena, V., Pillot, T., Davies, S. L., Bakrania, P., Matthews, D., Brownlees, J., Bouter, Y., & Bayer, T. A.
Affiliations
  • Universitätsmedizin Göttingen (DE)
  • Heinrich Heine University Düsseldorf (DE)
  • LifeArc (GB)
Corresponding author
Bayer, Thomas A.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-12-02
Volume
5
Issue
1
Pages
17338-17338
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep17338
PMC
PMC4667289
OpenAlex
W2187444064
Cited by
61
References
45
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 3
FWCI
4.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • GRO (submittedVersion, cc-by)
Funders
  • Alzheimer Forschung Initiative
  • Studienstiftung des Deutschen Volkes
  • Medical Research Council (MC_G1000806)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, amyloid-beta, pyroglutamate amyloid-beta, Fab fragment, passive immunization, amyloid plaques, spatial reference memory, working memory, 5xFAD mice, neuroprotection
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Humans, Immunization, Passive, Peptide Fragments, Amyloid beta-Peptides, Mice, Rats, Antibodies, Monoclonal, Murine-Derived

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