Copyright: © 2026 by the authors. Licensee: Pirogov University.
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ORIGINAL RESEARCH

Optimal HAEE synthetic peptide therapeutic dose with repeated administration to APP/PS1 mice

Kozin SA1 , Lysikova EA2 , Yakovlev RYu3 , Mukhina KA1 , Soloveva AE2 , Shmigol TA2 , Makarov AA1 , Mitkevich VA1
About authors

1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

2 Pirogov Russian National Research Medical University, Moscow, Russia

3 Scientific Centre RTA LLC, Moscow, Russia

Correspondence should be addressed: Vladimir A. Mitkevich
Vavilova, 32, Moscow, 119991; ur.bmie@hcivektim

About paper

Funding: the study was supported by the Ministry of Health of the Russian Federation, topic: Pharmaceutical Development and Preclinical Trials of the Peptide Drug for Treatment of Alzheimer's Disease, 125022602911-9.

Acknowledgements: the authors would like to express their gratitude to E.V. Myachin, Chairman of the VSE Cooperative (Moscow, Russia), for providing the HAEE lyophilized synthetic peptide.

Author contribution: Kozin SA — study design, literature review, manuscript writing; Lysikova EA — experimental research involving APP/PS1 mice, проведение transcardial perfusion, histochemical analysis; Yakovlev RYu — analysis of the input HAEE synthetic peptide samples; Mukhina KA, Soloveva АЕ, Shmigol TA — experimental research involving APP/PS1 mice, preparation of brain slices, fluorescence microscopy image acquisition and analysis; Makarov AA, Mitkevich VA — study design, manuscript writing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Engelhardt Institute of Molecular Biology RAS (protocol No. 3 dated 11 September 2025) and conducted in accordance with guidelines for working with laboratory animals.

Received: 2025-12-09 Accepted: 2026-01-19 Published online: 2026-02-04
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Fig. Congophilic amyloid plaques in the typical brain section from the intact transgenic APP/PS1 mouse aged five months. А. Fluorescence signal after Congo red staining. B. Combined Congo red fluorescence and transmitted light microscopy images. The dotted line indicates the CA1, CA3 areas and the DG (dentate gyrus). Scale — 500 µm
Table. Inhibition of the congophilic amyloid plaque formation in the hippocampal areas СА1, СА2, СА3 and the dentate gyrus in transgenic APP/PS1 mice receiving repeated subcutaneous injections of the drugs based on the Ac-His-Ala-Glu-Glu-NH2 (HAEE) synthetic peptide prepared in 125 µL of normal saline and differing in the dose of the administered peptide