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23.10.2024
32 5 minutes read

Болезнь Альцгеймера – это наиболее распространенная форма деменции и одна из главных загадок современной нейронауки. Несмотря на десятилетия исследований, многие аспекты того, как именно это нейродегенеративное заболевание разрушает мозг, остаются неясными. Традиционно считалось, что недуг, от которого страдают как минимум 10 миллионов человек по всему миру (по данным Всемирной организации здравоохранения), развивается поэтапно путем воспаления, гибели клеток и накоплением белков в виде бляшек. Все эти процессы приводят к деградации памяти, поведения и мышления. Теперь же команда ученых из Института Аллена в Сиэтле (США) и других учреждений обнаружила, что заболевание разрушает мозг в два этапа – первая фаза происходит незаметно, до проявления симптомов, а вторая характеризуется непосредственным разрушением мозга.

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Новаторский генетический анализ предоставил новые данные о том, как болезнь Альцгеймера повреждает мозг. Изображение: news.mit.edu

Содержание

  • 1 Два этапа, которые разрушают мозг
  • 2 Повреждение тормозных нейронов
  • 3 Мультимодальная карта и повреждение мозга
  • 4 Что дальше?

Два этапа, которые разрушают мозг

В работе, недавно опубликованной в журнале Nature Neuroscience, представлен революционный взгляд на то, как именно прогрессирует болезнь Альцгеймера и какие клетки мозга наиболее к ней уязвимы. Проанализировав образцы ткани мозга, полученных посмертно у доноров с подтвержденным диагнозом, исследовательская группа выяснила, что болезнь прогрессирует в два отчетливых этапа.

Первый этап (фаза) характеризуется медленным увеличением воспаления. Это означает, что постепенное нарастание воспалительных процессов в мозге происходит незаметно, без проявления таких симптомов, как нарушение памяти и мышления. Примечательно, что первая фаза поражает только определенные клетки – тормозные нейроны (о них поговорим позже).

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Болезнь Альцгеймера прогрессирует в два этапа. Изображение: newsnetwork.mayoclinic.org

Стремительное повреждение мозга происходит на втором этапе развития болезни и сопровождается проявлением симптомов, путем накопления в мозге бляшек бета-амилоида и нейрофибриллярных клубков тау-белка (напомним, бляшки бета-амилоида прерывают активность, которая поддерживает нормальное функционирование клеток мозга, а скопления тау-белка внутри нейронов убивает клетки). Эти процессы разрушают нейронные цепи и приводят к потере когнитивных функций.

Больше по теме: Болезнь Альцгеймера может поразить даже 19-летних — вот доказательство

Повреждение тормозных нейронов

Команда проанализировала генетическую активность отдельных клеток, извлеченных из средней височной извилины – области мозга, которая принимает активное участие в обработке языка и семантической памяти. В общей сложности были изучены образцы более 3,4 миллиона ядер клеток, полученных от 84 доноров с болезнью Альцгеймера на разных стадиях. Средний возраст доноров составил 88 лет, из них 51 женщина и 33 мужчины.

Затем, вместо того, чтобы сравнить проанализированные ткани с тканями здоровых людей, команда оценила количественную нейропатологию доноров и расположила их по шкале псевдопрогрессии заболевания – то есть по мере проявления симптомов и повреждения мозга – и разработала мультимодальную карту клеток мозга при болезни Альцгеймера, которая отражает генетическую и клеточную хронологию изменений на протяжении всего заболевания.

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Генетический анализ клеток мозга позволил выявить типы клеток, которые в первую очередь могут пострадать от болезни. Изображение: Courtesy of The Allen Institute, Seattle

Таким образом ученые смогли выявить конкретные типы клеток, которые первыми попадают под удар этой формы деменции – так называемые тормозные нейроны, которые играют ключевую роль в регулировании активности мозга, деактивируя или успокаивая другие нейроны. Это самая захватывающая часть открытия: ранее большинство исследований фокусировалось на возбуждающих нейронах (клетках мозга, которые активируют другие нейроны).

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Результаты анализа показали, что специфическое повреждение тормозных нейронов на первом этапе развития болезни Альцгеймера нарушает нейронные цепи, способствуя серьезному повреждению мозга на втором этапе. Открытие позволит диагностировать заболевание до проявления симптомов и разработать новые терапевтические стратегии и препараты, направленные на предотвращение или замедление прогрессирования болезни до необратимых повреждений мозга.

Мультимодальная карта и повреждение мозга

Создание мультимодальной карты клеток мозга (или атласа под названием Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD)) позволило получить всестороннее понимание того, какие именно клеточные типы наиболее уязвимы и где именно в микроструктуре ткани расположены. Открытие стало возможным благодаря объединению различных типов данных (геномных, транскриптомных, эпигеномных и пространственных).

Интересно, что в первой фазе развития заболевания также наблюдается активация микроглии — иммунных клеток мозга и реактивных астроцитов. С одной стороны это означает, что мозг пытается защититься от начальных повреждений, с другой — возможное усиление воспаления и дальнейшее повреждение нейронов.

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Болезнь Альцгеймера не лечится. Все, что можно сделать сегодня – замедлить ее прогрессирование. Изображение: newscientist.com

Во второй, более стремительной фазе болезни, происходит экспоненциальное увеличение патологии. Это означает, что накопление бляшек бета-амилоидов и нейрофибриллярных клубков тау-белка приводит к серьезным повреждением нейронов и выраженной потере когнитивных функций. Для второго этапа болезни также характерна потеря возбуждающих нейронов и других типов тормозных нейронов.

Вам будет интересно: Ученые определили четыре типа болезни Альцгеймера

Понимание того, что болезнь Альцгеймера прогрессирует в два четких этапа, и идентификация клеточных типов, поражаемых на каждой стадии, предоставляет новые возможности для разработки целенаправленных терапевтических стратегий. Например, лечение, направленное на снижение воспаления и защиту тормозных нейронов на ранней стадии, может замедлить или предотвратить дальнейшее развитие недуга.

Полученные результаты фундаментально меняют наше понимание того, как именно болезнь Альцгеймера повреждает мозг и способствуют разработке новых методов лечения этого нейродегенеративного заболевания, – отметил директор Национального института старения (NIH) Ричард Ходес, который не принимал участия в исследовании.

Немаловажно, что полученные в рамках нового исследования данные нашли подтверждение в других крупных исследованиях, что укрепляет достоверность и значение новой научной работы. Таким образом, по мере развития технологий возможности по изучению одной из самых сложных для понимания нейродегенеративных болезней увеличиваются.

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Болезнь Альцгеймера – тяжелая форма деменции. Изображение: dementech.com

Современные методы секвенирования генома и пространственной транскриптомики позволяет ученым картировать изменения в мозге на клеточном уровне и выявлять ранее неизвестные фазы болезни, наряду с новыми потенциальными «мишенями» для вмешательства и терапии.

Не пропустите: Жить дольше и вылечить болезнь Альцгеймера помогут низкие температуры

Что дальше?

Результаты нового исследования – это значительный шаг вперед в понимании болезни Альцгеймера, а создание мультмодальной карты позволяет ученым увидеть более полную картину того, как болезнь влияет на мозг на микроуровне. Хотя впереди еще много работы, особенно в области разработки новейших методов лечения, такие исследования приближают нас к разгадке тайн этой сложной болезни и открывают новые пути для вмешательства.

Теперь, когда ученые имеют более четкое представление о том, какие клеточные типы и процессы вовлечены в ранние стадии болезни, следующим шагом станет разработка диагностических инструментов для выявления этих изменений у живых пациентов. Такой подход может включать в себя разработку биомаркеров или визуализационных методов, которые позволят обнаружить раннее воспаление или потерю тормозных нейронов.Терапевтические стратегии, направленные на сохранение функции тормозных нейронов, также могут оказаться перспективными.

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Победа над деменцией – непростая задача. Изображение: alzheimer.ie

Болезнь Альцгеймера – одна из самых серьезных медицинских проблем. Заболевание, впервые описанное в 1907 году немецким психиатром Алоисом Альцгеймером, не излечимо, однако ученые надеются, что рано или поздно смогут ее победить. Безусловно, успех в борьбе с недугом требует совместных усилий исследователй из разных областей науки и медицины. Расширение общедоступных ресурсов, таких как новая мультимодальная карта, способствует обмену знаниями и ускоряет прогресс в этой области.

А вы знали, что повторяющиеся негативные мысли связали с болезнью Альцгеймера? Подробности можно прочитать здесь!

Хотя впереди у ученых и врачей долгий путь, результаты нового исследования приближают нас к дню, когда болезнь Альцгеймера станет излечимым или даже предотвратимым состоянием. Понимание того, как она развивается на клеточном уровне, открывает двери для новых возможностей и внушает оптимизм в отношении здорового старения.

Источник

23.10.2024
32 5 minutes read
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12.06.2024

Тайна Аль-Наслаа: кто идеально разрезал скалу посреди пустыни? — Hi-News.ru»>/**/ article{display:block}body{font-size:14px;line-height:1}ol,ul{list-style:none;padding:0;margin:0}html,body{font:400 -apple-system,BlinkMacSystemFont,sans-serif}html,body,div,span,iframe,h1,p,a,img,ins,strong,b,form,article,time{margin:0;padding:0;border:0;font-size:100%;-webkit-text-size-adjust:100%;font-family:-apple-system,BlinkMacSystemFont,sans-serif;vertical-align:baseline;-webkit-font-smoothing:antialiased}body{font-size:14px;line-height:1;min-width:1124px}ol,ul{list-style:none;padding:0;margin:0}b,strong{font-weight:700}img{overflow:hidden;height:auto;max-width:100%;font:400 10px -apple-system,BlinkMacSystemFont,sans-serif}p{color:#000;margin-bottom:15px;font:400 20px/1.5 -apple-system,BlinkMacSystemFont,sans-serif}h1{color:#000;margin:0 0 28px 0;font:700 54px/1 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17.12.2023

Каким был климат на Марсе до того, как планета лишилась атмосферы — Hi-News.ru»>/**/ article{display:block}body{font-size:14px;line-height:1}ol,ul{list-style:none;padding:0;margin:0}html,body{font:400 -apple-system,BlinkMacSystemFont,sans-serif}html,body,div,span,iframe,h1,p,a,img,ins,strong,b,form,article,time{margin:0;padding:0;border:0;font-size:100%;-webkit-text-size-adjust:100%;font-family:-apple-system,BlinkMacSystemFont,sans-serif;vertical-align:baseline;-webkit-font-smoothing:antialiased}body{font-size:14px;line-height:1;min-width:1124px}ol,ul{list-style:none;padding:0;margin:0}b,strong{font-weight:700}img{overflow:hidden;height:auto;max-width:100%;font:400 10px -apple-system,BlinkMacSystemFont,sans-serif}p{color:#000;margin-bottom:15px;font:400 20px/1.5 -apple-system,BlinkMacSystemFont,sans-serif}h1{color:#000;margin:0 0 28px 0;font:700 54px/1 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27.01.2024

Самый длинный автобусный маршрут, который продлился 50 дней — Hi-News.ru»>/**/ article{display:block}body{font-size:14px;line-height:1}ol,ul{list-style:none;padding:0;margin:0}html,body{font:400 -apple-system,BlinkMacSystemFont,sans-serif}html,body,div,span,iframe,h1,p,a,img,ins,strong,b,form,article,time{margin:0;padding:0;border:0;font-size:100%;-webkit-text-size-adjust:100%;font-family:-apple-system,BlinkMacSystemFont,sans-serif;vertical-align:baseline;-webkit-font-smoothing:antialiased}body{font-size:14px;line-height:1;min-width:1124px}ol,ul{list-style:none;padding:0;margin:0}b,strong{font-weight:700}img{overflow:hidden;height:auto;max-width:100%;font:400 10px -apple-system,BlinkMacSystemFont,sans-serif}p{color:#000;margin-bottom:15px;font:400 20px/1.5 -apple-system,BlinkMacSystemFont,sans-serif}h1{color:#000;margin:0 0 28px 0;font:700 54px/1 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02.09.2024