Features of expression of ß-amyloid in cerebral endothelial cells in experimental Alzheimer’s disease


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Abstract

Introduction. The formation of neurofibrillary plexuses and the accumulation of senile plaques in the parenchyma and cerebral vessels are the key pathological signs of Alzheimer’s disease presenting a neurodegenerative disease. The main component of senile plaques is ß-amyloid. The aim of the study. To study the expression of ß-amyloid in cells of cerebral endothelium of the hippocampus in experimental Alzheimer’s disease in vivo, to evaluate the production of ß-amyloid precursor protein (APP) upon RAGE and CD147 modulation in the cerebral vascular endothelium as part of the BBB model in vitro. Methods. Male mice of lines the B6SLJ-Tg(APPSwFlLon, PSEN1 * M146L * L286V) 6799Vas (genetic model of Alzheimer’s disease) and C57BL / 6 (control group) at the age of 9 months. Male mice of the line the C57BL / 6 at the age of 4 months, which were introduced ß-amyloid for modeling Alzheimer’s disease, sham-operated animals were used as a control. The expression of ß-amyloid in the hippocampus was studied by immunohistochemistry. Quantitative analysis of APP gene expression in vitro was performed by PCR. Results. The expression of ß-amyloid in the endothelium of the hippocampus was significantly (р<0.001) increased both in animals with ß-amyloid administration compared to the group of sham-operated animals, and in animals with a genetic model of Alzheimer’s disease compared to the control group (р<0.0001). It was found that blocking the expression of RAGE reduces the production of APP, while the suppression of the expression of CD147 induces this process. However, the ligands of the RAGE and CD147 receptors - Ab1-42 and cyclophilin A, respectively, show the opposite effect. Conclusion. Alzheimer’s disease is accompanied by an increase in the level of ß-amyloid in the endothelium of the hippocampus, which indicates the activation of APP processing with the generation of neurotoxic ß-amyloid. This causes destructive changes in the endothelium, contributing to an increase in BBB permeability and disease progression. Exposure to RAGE and CD147 chemical modulators can affect APP production. This makes it possible to correct the negative course of the disease.

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About the authors

Yana Valerievna Gorina

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Associate Professor of the Department of Biochemistry, Associate professor, candidate of pharmaceutical sciences Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

Elena Dmitrievna Osipova

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: elena.hilazheva@mail.ru
Senior Lecturer, Department of Biochemistry Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

Audrey Vasilievich Morgun

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: 441682@mail.ru
Associate Professor of the Department of Pediatrics IPO, Doctor of medical sciences Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

Olga Leonidovna Lopatina

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: ol.lopatina@gmail.com
Professor of the Department of Biochemistry, Associate professor, doctor of biological sciences Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

Ekaterina Viktorovna Kharitonova

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: ekaterinav1201@gmail.com
Senior Lecturer, Department of Biochemistry, Candidate of pharmaceutical sciences. Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

Alla Borisovna Salmina

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: allasalmina@mail.ru
Professor, Head of the Department of Biochemistry, Head of the Research Institute of Molecular Medicine and Pathobiochemistry,Professor, doctor of medical sciences Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

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