Proteomic Spectrum of Serum Exosomes in Ischemic Stroke Patients Is Associated with Cognitive Impairment in the Post-Stroke Period

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Tatyana A. Druzhkova¹, Marina Yu. Zhanina^1,2, Elena E. Vladimirova³, Alla B. Guekht^1,4, Natalia V. Gulyaeva^1,2,a*

¹Moscow Research and Clinical Center for Neuropsychiatry, 115419 Moscow, Russia

²Department of Functional Biochemistry of Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia

³M. P. Konchalovsky City Clinical Hospital, 124489 Moscow, Russia

⁴Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, 119049 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 1, 2024; Revised: August 8, 2024; Accepted: September 1, 2024

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Ischemic stroke (IS) and subsequent neuropsychiatric disorders are among the leading causes of disability worldwide. Several strategies have been previously proposed to utilize exosomes for assessing the risk of IS-related diseases. The aim of this work was to evaluate serum exosomal proteins in IS patients during the chronic post-stroke period and to search for their associations with the development of post-stroke mild cognitive impairment (MCI). Comparative quantitative proteomic analysis of serum exosomes of patients without post-stroke MCI (19 patients mean age 52.0 ± 8.1 years) and patients with post-stroke MCI (11 patients, mean age 64.8 ± 5.6 years) revealed significant differences in the levels of 62 proteins out of 186 identified. Increased levels of the proteins associated with immune system and decreased levels of the proteins involved in lipid metabolism were observed in the patients with MCI compared to the patients without MCI in the chronic post-stroke period. The obtained data suggest that the higher level of immune system activation in the patients during a relatively long period after IS may be one of the risk factors for the development of post-stroke cognitive disorders and suggest participation of exosomal transport in these processes.

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KEY WORDS: exosomes, serum, ischemic stroke, mass spectrometry, proteomic analysis, post-stroke cognitive impairment, immune system

DOI: 10.1134/S0006297924090062

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