Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice

Kassenova, Aliya; Svirin, Evgeniy; Sitdikova, Kseniia; Chaprov, Kirill; Tsoy, Andrey; Munter, Johannes de P.M.; Nurzhanov, Anuar; Kuznetsova, Maria; Veremeyko, Tatyana; Deykin, Alexey; Ponomarev, Eugene D.; Strekalova, Tatyana; Askarova, Sholpan

doi:10.3390/ijms27114994

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Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice

by

Aliya Kassenova

^1,2,†

,

Evgeniy Svirin

^3,†

,

Kseniia Sitdikova

⁴

,

Kirill Chaprov

⁴

,

Andrey Tsoy

¹

,

Johannes de P.M. Munter

⁵

,

Anuar Nurzhanov

⁶

,

Maria Kuznetsova

⁷

,

Tatyana Veremeyko

⁶,

Alexey Deykin

⁸,

Eugene D. Ponomarev

^6,9,10,

Tatyana Strekalova

^11,*,‡ and

Sholpan Askarova

^1,7,*,‡

¹

Center for Life Sciences, National Laboratory Astana, Nazarbayev University, 010000 Astana, Kazakhstan

²

Department of General Biology and Genomics, Faculty of Natural Sciences, L. N. Gumilyov Eurasian National University, 010000 Astana, Kazakhstan

³

Center for Neurocognitive Research (MEG-Center), Moscow State University of Psychology and Education, 123290 Moscow, Russia

⁴

Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 119071 Chernogolovka, Russia

⁵

Neuroplast B.V., 6222 NK Maastricht, The Netherlands

⁶

Department of Biology, School of Sciences and Humanities, Nazarbayev University, 010000 Astana, Kazakhstan

⁷

Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia

⁸

Laboratory of Genetic Technology and Gene Editing for Biomedicine and Veterinary, National Research Belgorod State University, 308015 Belgorod, Russia

⁹

Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong

¹⁰

Department of Biological Sciences and Bioinformatics, Xi’an Jiaotong-Liverpool University, Suzhou 215123, China

¹¹

Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitsinsel 50, 6229 ER Maastricht, The Netherlands

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^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work as first authors.

^‡

These authors contributed equally to this work as last authors.

Int. J. Mol. Sci. 2026, 27(11), 4994; https://doi.org/10.3390/ijms27114994

Submission received: 17 April 2026 / Revised: 25 May 2026 / Accepted: 28 May 2026 / Published: 30 May 2026

(This article belongs to the Section Molecular Neurobiology)

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Abstract

Growing evidence suggests an important pathogenetic role of brain-specific gangliosides in the mechanisms underlying Alzheimer’s disease (AD), the most common form of dementia. Nutritional strategies targeting ganglioside sialylation—for example, through agglutinin-mediated modulation—have therefore attracted increasing research interest. In particular, wheat malt extract (WME), a food-derived source of wheat germ agglutinin (WGA) with high affinity for gangliosides, may influence molecular pathways involved in AD pathogenesis. Twelve-month-old female APPswe/PS1E9 transgenic mice, a model of AD, and wild-type (WT) littermates received WME or tap water for three weeks. Behavioral performance was subsequently assessed. Amyloid plaque burden and astrocyte activation were evaluated using Congo red staining and GFAP immunoreactivity, respectively. Gene expression of selected AD markers in the brain was quantified by RT–qPCR. Aged WT mice exhibited robust, region-specific molecular responses to WME, including upregulation of activity-dependent and synaptic plasticity genes (Arc, Egr1, Bdnf, Syp), enhancement of metabolic and insulin-related signaling (Pgc1a, Sirt1, Igf1r, Irs2), increased Cldn5 expression, and reduced pro-inflammatory Il1β expression. APP/PS1 mice exhibited limited response to WME, suggesting more persistent transcriptional signatures of synaptic impairment, metabolic dysregulation, and neuroinflammation than in WT mice. We found no significant effects of WME treatment on amyloid plaque density and behavior in APP/PS1 mice. No effects on astrocyte activation were observed in either group. These findings demonstrate that dietary WME counteracts abnormal behaviors and molecular changes in neuron plasticity, metabolic, and vascular markers under conditions of normal aging but fails to improve the hallmarks of AD pathology. This highlights the potential of WGA-containing nutrients as a preventive nutritional approach targeting pathogenic mechanisms of aging and, potentially, AD pathology.

Keywords: Alzheimer’s disease; APPswe/PS1E9 mice; wheat malt extract; wheat germ agglutinin

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MDPI and ACS Style

Kassenova, A.; Svirin, E.; Sitdikova, K.; Chaprov, K.; Tsoy, A.; Munter, J.d.P.M.; Nurzhanov, A.; Kuznetsova, M.; Veremeyko, T.; Deykin, A.; et al. Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice. Int. J. Mol. Sci. 2026, 27, 4994. https://doi.org/10.3390/ijms27114994

AMA Style

Kassenova A, Svirin E, Sitdikova K, Chaprov K, Tsoy A, Munter JdPM, Nurzhanov A, Kuznetsova M, Veremeyko T, Deykin A, et al. Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice. International Journal of Molecular Sciences. 2026; 27(11):4994. https://doi.org/10.3390/ijms27114994

Chicago/Turabian Style

Kassenova, Aliya, Evgeniy Svirin, Kseniia Sitdikova, Kirill Chaprov, Andrey Tsoy, Johannes de P.M. Munter, Anuar Nurzhanov, Maria Kuznetsova, Tatyana Veremeyko, Alexey Deykin, and et al. 2026. "Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice" International Journal of Molecular Sciences 27, no. 11: 4994. https://doi.org/10.3390/ijms27114994

APA Style

Kassenova, A., Svirin, E., Sitdikova, K., Chaprov, K., Tsoy, A., Munter, J. d. P. M., Nurzhanov, A., Kuznetsova, M., Veremeyko, T., Deykin, A., Ponomarev, E. D., Strekalova, T., & Askarova, S. (2026). Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice. International Journal of Molecular Sciences, 27(11), 4994. https://doi.org/10.3390/ijms27114994

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Effects of Wheat Malt Extract on Molecular and Behavioral Markers in Aged APP/PS1 and Wild-Type Mice

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