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APPswe/PS1dE9/Blg Transgenic Mouse Line for Modeling Cerebral Amyloid Angiopathy Associated with Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common proteinopathy, which is accompanied by a steady decrease in the patient’s cognitive functions with a simultaneous accumulation of amyloid plaques in brain tissues. Amyloid plaques are extracellular aggregates of amyloid β (Aβ) and are associated with neuroinflammation and neurodegeneration. Unlike humans and all other mammals, rats and mice do not reproduce AD-like pathology because there are three amino acid substitutions in their Aβ. Amyloid plaques form in the brains of transgenic mice with overexpression of human Aβ, and such mice are therefore possible to use in biomedicine to model the key features of AD. The transgenic mouse line APPswe/PS1dE9 is widely used as an animal model to study the molecular mechanisms of AD. A study was made to characterize the APPswe/PS1dE9/Blg subline, which was obtained by crossing APPswe/PS1dE9 mice on a CH3 genetic background with C57Bl6/Chg mice. No difference in offspring’s survival and fertility was observed in the subline compared to wild-type control mice. Histological analysis of the brain in the APPswe/PS1dE9/Blg line confirmed the main neuromorphological features of AD and showed that amyloid plaques progressively increase in number and size during aging. The APPswe/PS1dE9/Blg line was assumed to provide a convenient model for developing therapeutic strategies to slow down AD progression.

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Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2021-1346). Animal procedures were funded by the State Task of the Laboratory of Genetic Technologies and Genome Editing for Biomedicine and Animal Health—FZWG-2021-0016

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Authors and Affiliations

  1. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432, Chernogolovka, Russia

    E. A. Lysikova & K. D. Chaprov

  2. Belgorod State University, 308015, Belgorod, Russia

    E. V. Kuzubova, A. I. Radchenko, E. A. Patrakhanov, K. D. Chaprov, M. V. Korokin, A. V. Deykin, O. S. Gudyrev & M. V. Pokrovskii

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  1. E. A. Lysikova
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  2. E. V. Kuzubova
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  3. A. I. Radchenko
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  4. E. A. Patrakhanov
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  5. K. D. Chaprov
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  6. M. V. Korokin
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  7. A. V. Deykin
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  8. O. S. Gudyrev
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  9. M. V. Pokrovskii
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Correspondence to E. A. Lysikova.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement of the welfare of animals. Experiments with animals obeyed the “Rules of Laboratory Practice in the Russian Federation” (no. 199n dated April 1, 2016). The study was approved by the Ethics Committee at the Belgorod State University (Minutes no. 02.21-4 dated February 8, 2021).

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Translated by T. Tkacheva

Abbreviations: AD, Alzheimer’s disease; APP, amyloid precursor protein; PSEN1, presenilin 1.

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Lysikova, E.A., Kuzubova, E.V., Radchenko, A.I. et al. APPswe/PS1dE9/Blg Transgenic Mouse Line for Modeling Cerebral Amyloid Angiopathy Associated with Alzheimer’s Disease. Mol Biol 57, 74–82 (2023). https://doi.org/10.1134/S0026893323010077

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