morphoМорфологические ведомостиMorphological newsletter1812-31712686-8741Private Medical University REAVIZ10.20340/mv-mn.2026.34(2).1021morpho-1051Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯRESEARCH ARTICLESИММУНОГИСТОХИМИЧЕСКАЯ ОЦЕНКА МАРКЕРОВ АУТОФАГИИ В ГИППОКАМПЕ ЧЕЛОВЕКА ПРИ СТАРЕНИИ И БОЛЕЗНИ АЛЬЦГЕЙМЕРАIMMUNOHISTOCHEMICAL EVALUATION OF AUTOPHAGY MARKERS IN THE HUMAN HIPPOCAMPUS DURING AGING AND ALZHEIMER'S DISEASEhttps://orcid.org/0000-0002-0552-6939СухоруковВ. С.SukhorukovV. S.

Сухоруков Владимир Сергеевич, доктор медицинских наук, профессор

Москва

Vladimir S. Sukhorukov, Doctor of Medical Sciences, Professor

Moscow

vsukhorukov@gmail.comhttps://orcid.org/0000-0002-8999-9986БараничТ. И.BaranichT. I.

Баранич Татьяна Ивановна, кандидат медицинских наук

Москва

Tat′yana I. Baranich, Candidate of Medical Sciences

Moscow

atyana@mail.ruhttps://orcid.org/0009-0003-0223-7335ВельцО. В.VeltsО. V.

Вельц Ольга Владимировна

Москва

Ol′ga V. Vel′ts

Moscow

welzolg@mail.ruhttps://orcid.org/0009-0009-8464-9766ОкуловаК. М.OkulovaK. M.

Окулова Ксения Максимовна

Москва

Kseniya M. Okulova

Moscow

kseniaokul2101@gmail.comhttps://orcid.org/0000-0001-5222-5322ВоронковД. Н.VoronkovD. N.

Воронков Дмитрий Николаевич, кандидат медицинских наук

Москва

Dmitriy N. Voronkov, Candidate of Medical Sciences, Senior Researcher

Moscow

voronkovdm@gmail.comhttps://orcid.org/0000-0001-7112-2556ЕгороваА. В.EgorovaA. V.

Егорова Анна Валериевна, Российский центр неврологии и нейронаук

Москва

Anna V. Yegorova, Researcherin

Moscow

av_egorova@bk.ruhttps://orcid.org/0009-0006-0346-4523ЩербакЕ. В.ShcherbakE. V

Щербак Екатерина Вадимовна

Москва

Yekaterina V. Shcherbak

Moscow

scherbakev2@zdrav.mos.ruhttps://orcid.org/0000-0001-8708-6940ГлинкинаВ. В.GlinkinaV. V.

Глинкина Валерия Владимировна, доктор медицинских наук, профессор

Москва

Valeriya V. Glinkina, Doctor of Medical Sciences, Professor

Moscow

vglinkina@mail.ruРоссийский центр неврологии и нейронаук; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияRussian Center of Neurology and Neurosciences; Pirogov Russian National Research Medical UniversityRussian FederationРоссийский центр неврологии и нейронаук; Первый Московский государственный медицинский университет имени И.М. СеченоваРоссияRussian Center of Neurology and Neurosciences; Sechenov First Moscow State Medical UniversityRussian FederationРоссийский центр неврологии и нейронаукРоссияRussian Center of Neurology and NeurosciencesRussian FederationГородская клиническая больница № 1 имени Н.И. ПироговаРоссияPirogov City Clinical Hospital No. 1Russian Federation2026300720263422840Copyright © Сухоруков В.С., Баранич Т.И., Вельц О.В., Окулова К.М., Воронков Д.Н., Егорова А.В., Щербак Е.В., Глинкина В.В., 20262026Сухоруков В.С., Баранич Т.И., Вельц О.В., Окулова К.М., Воронков Д.Н., Егорова А.В., Щербак Е.В., Глинкина В.В.Sukhorukov V.S., Baranich T.I., Velts О.V., Okulova K.M., Voronkov D.N., Egorova A.V., Shcherbak E.V., Glinkina V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.morpholetter.com/jour/article/view/1051

ВВЕДЕНИЕ. Аутофагия является ключевым механизмом удаления поврежденных органелл в нейронах, и ее дисфункция лежит в основе старения и патогенеза многих нейродегенеративных заболеваний, включая болезнь Альцгеймера. Однако специфические особенности аутофагии в различных областях гиппокампа, проявляющих избирательную уязвимость при болезни Альцгеймера, остаются недоста-точно изученными.ЦЕЛЬ: оценка маркеров аутофагии в нейронах зон CA1 и CA2 гиппокампа человека в процессе физио-логического старения и при спорадической болезни Альцгеймера.МАТЕРИАЛЫ И МЕТОДЫ. Работа проведена на аутопсийном материале трупов молодых людей (35–45 лет, n=20), пожилых людей без нейродегенеративных заболеваний (>85 лет, n=20) и людей с бо-лезнью Альцгеймера (стадия по Браак 3–4, >85 лет, n=15). Количество маркеров убиквитина pS65-Ub, TOMM20, SQSTM1/p62, Beclin-1, LC3b и LAMP2 определяли иммуногистохимическим методом, после чего оценивали интенсивность окрашивания в перикарионах нейронов.РЕЗУЛЬТАТЫ. Было установлено, что с возрастом компенсаторная активация маркеров аутофагии от-сутствует в зоне CA1 на фоне накопления адаптерного белка p62, тогда как в зоне CA2 наблюдается увеличение Beclin-1 и LAMP2 с уменьшением количества зрелых аутофагосом (LC3b). При болезни Аль-цгеймера в обеих зонах наблюдается уменьшение количества инициационных комплексов, содержа-щих Beclin-1, и накопление аутофагосом (LC3b); однако в зоне CA2 дополнительно регистрируется уменьшение количества LAMP2 и p62, что указывает на блокировку терминальных стадий аутофагии.ЗАКЛЮЧЕНИЕ. Полученные данные указывают на выраженную зональную гетерогенность аутофаги-ческого ответа в гиппокампе как в процессе старения, так и при болезни Альцгеймера. Выявленные различия в процессе аутофагии в зонах CA1 и CA2 подтверждают необходимость дифференцированно-го подхода к выбору таргетных препаратов для лечения нейродегенеративных изменений.

INTRODUCTION. Autophagy is a key mechanism for the removal of damaged organelles in neurons, and its dysfunction underlies aging and the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease. However, the specific features of the autophagic response in different hippocampal regions that ex-hibit selective vulnerability in Alzheimer's disease remain poorly understood.OBJECTIVE. The aim of this study was to comprehensively evaluate autophagy markers in neurons of the CA1 and CA2 zones of the human hippocampus during physiological aging and Alzheimer's disease.MATERIALS AND METHODS. The work was performed on autopsy material from young patients (35-45 years old, n=20), elderly patients without neurodegenerative pathology (>85 years old, n=20), and patients with Alzheimer's disease (Braak stage 3-4, >85 years old, n=15). Markers of ubiquitin, pS65-Ub, TOMM20, SQSTM1/p62, Beclin-1, LC3b, and LAMP2 were determined immunohistochemically, and staining intensity in the neuronal perikarya was assessed.RESULTS. It was found that, with age, compensatory activation of autophagy markers is absent in the CA1 zone against the background of accumulation of the adapter protein p62, whereas in the CA2 zone, an in-crease in Beclin-1 and LAMP2 is observed with a decrease in the number of mature autophagosomes (LC3b). In Alzheimer's disease, a decrease in the number of initiation complexes containing Beclin-1 and accumula-tion of autophagosomes (LC3b) are observed in both zones; however, in the CA2 zone, a decrease in the amounts of LAMP2 and p62 is additionally recorded, indicating a block in the terminal stages of autophagy.CONCLUSION. The obtained data indicate pronounced zonal heterogeneity of the autophagic response in the hippocampus both during aging and in Alzheimer's disease. The identified differences in the autophagy pro-cess in the CA1 and CA2 zones confirm the need for a differentiated approach to the selection of targeted drugs for the treatment of neurodegenerative changes.

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The authors declare that there are no conflicts of interest present.