medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2026.04.3-18medgen-3429Research ArticleНАУЧНЫЕ ОБЗОРЫREVIEWГенетические и молекулярные механизмы устойчивости к болезни АльцгеймераGenetic and molecular mechanisms of resistance to Alzheimer’s diseaseБичуринД. Р.BichurinD. R.

Бичурин Дамир Русланович 

430005, г. Саранск, ул. Большевистская, д. 68 

Damir R. Bichurin 

68 Bolshevistskaya str., Saransk 430005 

damir.bichur@yandex.ruЖуравлевМ. В.ZhuravlevM. V.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

МахкамовА. М.MakhkamovA. M.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

ИоноваЗ. А.IonovaZ. A.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

ЛобановаЕ. Г.LobanovaE. G.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

СтруковД. Д.StrukovD. D.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

СоколенкоС. А.SokolenkoS. A.

350063, г. Краснодар, ул. имени Митрофана Седина, 4 

4 Mitrofana Sedina str., Krasnodar, 350063 

РачковаД. М.RachkovaD. M.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

ХолматовХ. Дж.KholmatovKh. J.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

ЕрзинаД. Ш.ErzinaD. Sh.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

МатявинаЮ. М.MatyavinaYu. M.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

ЭфендиеваД. М.EfendievaD. M.

350063, г. Краснодар, ул. имени Митрофана Седина, 4 

4 Mitrofana Sedina str., Krasnodar, 350063 

АгаповД. С.AgapovD. S.

430005, г. Саранск, ул. Большевистская, д. 68 

68 Bolshevistskaya str., Saransk 430005 

Национальный исследовательский Мордовский государственный университет им. Н.П. ОгарёваРоссияNational Research Mordovia State UniversityRussian FederationКубанский государственный медицинский университетРоссияKuban State Medical UniversityRussian Federation202610052026254318Copyright © Бичурин Д.Р., Журавлев М.В., Махкамов А.М., Ионова З.А., Лобанова Е.Г., Струков Д.Д., Соколенко С.А., Рачкова Д.М., Холматов Х.Д., Ерзина Д.Ш., Матявина Ю.М., Эфендиева Д.М., Агапов Д.С., 20262026Бичурин Д.Р., Журавлев М.В., Махкамов А.М., Ионова З.А., Лобанова Е.Г., Струков Д.Д., Соколенко С.А., Рачкова Д.М., Холматов Х.Д., Ерзина Д.Ш., Матявина Ю.М., Эфендиева Д.М., Агапов Д.С.Bichurin D.R., Zhuravlev M.V., Makhkamov A.M., Ionova Z.A., Lobanova E.G., Strukov D.D., Sokolenko S.A., Rachkova D.M., Kholmatov K.J., Erzina D.S., Matyavina Y.M., Efendieva D.M., Agapov D.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3429

Болезнь Альцгеймера является наиболее распространённой формой нейродегенеративной деменции, характеризующейся накоплением β-амилоида, гиперфосфорилированного тау-белка и выраженной глиальной реакцией. Несмотря на интенсивное изучение патогенеза заболевания, эффективные патогенетические методы терапии остаются ограниченными. В последние годы особый интерес вызывают редкие генетические варианты, ассоциированные с естественной устойчивостью к болезни Альцгеймера. Наиболее изученными среди них являются варианты APOE3 Christchurch и RELN-COLBOS, обнаруженные у носителей мутации PSEN1 Glu280Ala в колумбийских семьях с аутосомно-доминантной формой заболевания. У этих пациентов когнитивное снижение было отсрочено более чем на два десятилетия по сравнению с типичными случаями, что указывает на наличие эндогенных механизмов нейропротекции. Обзор обобщает современные данные о роли вариантов APOE и RELN в регуляции сигнального каскада Reelin–ApoE, включающего белки DAB1, AKT и GSK3β, участвующие в контроле фосфорилирования тау и синаптической пластичности. Обсуждаются возможные механизмы влияния этих генетических факторов на активность микроглии, астроцитов и сохранение синаптических структур. Понимание молекулярных основ устойчивости мозга к болезни Альцгеймера открывает перспективы для разработки новых патогенетических стратегий, направленных на модуляцию Reelin–ApoE-зависимых путей и профилактику нейродегенерации.

Alzheimer’s disease is the most common form of neurodegenerative dementia characterized by β-amyloid accumulation, tau protein hyperphosphorylation, and pronounced glial activation. Despite extensive investigation of its pathogenesis, effective disease-modifying treatments remain limited. In recent years, rare genetic variants associated with innate resistance to Alzheimer’s disease have attracted growing attention. Among them, the APOE3 Christchurch and RELN-COLBOS variants identified in carriers of the PSEN1 Glu280Ala mutation in Colombian families with autosomal dominant Alzheimer’s disease are of particular interest. In these individuals, the onset of cognitive impairment was delayed by more than two decades compared to typical cases, suggesting the existence of endogenous neuroprotective mechanisms. This review summarizes current data on the role of APOE and RELN variants in the regulation of the Reelin– ApoE signaling cascade, involving DAB1, AKT, and GSK3β proteins that control tau phosphorylation and synaptic plasticity. Potential mechanisms by which these genetic factors modulate microglial and astrocytic activity and preserve synaptic integrity are discussed. Understanding the molecular basis of brain resistance to Alzheimer’s disease provides promising avenues for the development of new pathogenetic strategies aimed at modulating Reelin–ApoE-dependent pathways and preventing neurodegeneration.

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