Is Alzheimer disease a disease?

文献信息

DOI	10.1038/s41582-024-00940-4
PMID	38424454
期刊	Nature reviews. Neurology
影响因子	33.1
JCR 分区	Q1
发表年份	2024
被引次数	53
关键词	阿尔茨海默病, 神经退行性疾病, 淀粉样β蛋白, 神经纤维缠结, 多因素治疗
文献类型	Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
ISSN	1759-4758
页码	245-251
期号	20(4)
作者	Amos D Korczyn, Lea T Grinberg

一句话小结

痴呆症，尤其是阿尔茨海默病（AD），在老年人中普遍存在，但目前尚未找到有效的治愈方法。研究表明，AD的复杂性不仅涉及淀粉样-β斑块和tau蛋白缠结，还与多种遗传和环境因素相关，因此需要综合多种策略来识别、分类和治疗该病症，而非依赖单一疗法。

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阿尔茨海默病 · 神经退行性疾病 · 淀粉样β蛋白 · 神经纤维缠结 · 多因素治疗

摘要

痴呆症是老年人中常见的一种疾病，具有深远的社会影响。大量研究表明，尚未找到被认为是最常见的痴呆症——阿尔茨海默病（AD）的治愈方法。AD 的特征在于特定的大脑异常，即淀粉样-β斑块和tau蛋白神经纤维缠结，这些异常被认为会积极影响神经退行性过程。然而，目前缺乏关于淀粉样-β毒性的确凿证据，导致斑块和缠结积累的机制尚不明确，而去除淀粉样-β并未阻止神经退行性变。因此，问题仍然存在：我们在寻找解决方案的过程中取得了进展吗？AD 的复杂性体现在众多的遗传和环境风险因素以及多样的临床表现上，这表明 AD 更像是一种综合征，而不是传统意义上的疾病，其病理表现代表了一系列致病通路的汇聚。因此，解决方案需要采用多方面的方法，而非单一的“灵丹妙药”。对在斑块和缠结积累中汇聚的病症的更好识别和分类及其治疗，需要同时使用多种策略。

英文摘要

Dementia, a prevalent condition among older individuals, has profound societal implications. Extensive research has resulted in no cure for what is perceived as the most common dementing illness: Alzheimer disease (AD). AD is defined by specific brain abnormalities - amyloid-β plaques and tau protein neurofibrillary tangles - that are proposed to actively influence the neurodegenerative process. However, conclusive evidence of amyloid-β toxicity is lacking, the mechanisms leading to the accumulation of plaques and tangles are unknown, and removing amyloid-β has not halted neurodegeneration. So, the question remains, are we making progress towards a solution? The complexity of AD is underscored by numerous genetic and environmental risk factors, and diverse clinical presentations, suggesting that AD is more akin to a syndrome than to a traditional disease, with its pathological manifestation representing a convergence of pathogenic pathways. Therefore, a solution requires a multifaceted approach over a single 'silver bullet'. Improved recognition and classification of conditions that converge in plaques and tangle accumulation and their treatment requires the use of multiple strategies simultaneously.

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主要研究问题

核心洞察

研究背景和目的

阿尔茨海默病（AD）是老年人中普遍存在的一种疾病，具有深远的社会影响。尽管进行了大量研究，但至今尚无治愈方案。AD的特征是特定的脑部异常，包括淀粉样β（amyloid-β）斑块和tau蛋白神经纤维缠结，这些异常被认为对神经退行性过程产生积极影响。然而，关于淀粉样β毒性的确凿证据缺乏，导致斑块和缠结积累的机制仍不清楚，去除淀粉样β并未阻止神经退行。因此，本研究旨在探讨AD的复杂性及其潜在解决方案。

主要方法/材料/实验设计

本研究采用文献综述的方法，分析AD的病理特征、风险因素及其临床表现，强调多重因素对AD的影响。研究通过综合不同的研究结果，提出了一种多层次的解决方案。

以下是研究的技术路线示意图：

关键结果和发现

AD被视为一种综合征而非传统疾病，其病理表现源于多条致病途径的汇聚。
识别和分类与斑块及缠结积累相关的多种情况，对于制定有效的治疗方案至关重要。
目前的研究表明，单一的治疗策略（如去除淀粉样β）并不足以应对AD的复杂性，需采用多种策略同时进行。

主要结论/意义/创新性

本研究强调了阿尔茨海默病的复杂性，认为其更像是一种综合征，解决方案应采取多层次的方法。研究指出，未来的治疗需要同时考虑遗传和环境因素的影响，并综合多种治疗策略，以期更有效地应对AD。

研究局限性和未来方向

本研究主要基于文献综述，缺乏原始实验数据，可能影响结论的普适性。
未来研究应集中在探索淀粉样β斑块和tau蛋白缠结的形成机制，并开发多种靶向治疗策略，以提高对AD的治疗效果。
还需进行更大规模的临床试验，以验证多重治疗策略的有效性。

参考文献

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Incidence of Dementia over Three Decades in the Framingham Heart Study. - Claudia L Satizabal;Alexa S Beiser;Vincent Chouraki;Geneviève Chêne;Carole Dufouil;Sudha Seshadri - The New England journal of medicine (2016)
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... (43 更多篇文献)

Is Alzheimer disease a disease? ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​