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文献精选 > 近年高分"阿尔茨海默病"研究（IF≥30，近5年）

Alzheimer disease. ​

文献信息 ​

DOI10.1038/s41572-021-00269-y
PMID33986301
期刊Nature reviews. Disease primers
影响因子60.6
JCR 分区Q1
发表年份2021
被引次数954
关键词阿尔茨海默病, β-淀粉样蛋白, 神经退行性疾病, 认知障碍
文献类型Journal Article, Research Support, N.I.H., Extramural, Review
ISSN2056-676X
页码33
期号7(1)
作者David S Knopman, Helene Amieva, Ronald C Petersen, Gäel Chételat, David M Holtzman, Bradley T Hyman, Ralph A Nixon, David T Jones

一句话小结 ​

本研究探讨了阿尔茨海默病（AD）的生物学机制，指出其主要表现为β-淀粉样蛋白斑块和tau蛋白神经纤维缠结的形成，导致突触稳态丧失及内质体/溶酶体功能障碍。该研究为理解AD的病理过程及寻找有效治疗靶点提供了重要基础。

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阿尔茨海默病 · β-淀粉样蛋白 · 神经退行性疾病 · 认知障碍

摘要 ​

阿尔茨海默病（AD）在生物学上定义为存在β-淀粉样蛋白斑块和tau蛋白神经纤维缠结。阿尔茨海默病是一种遗传性和散发性的神经退行性疾病，其典型表现为遗忘性认知障碍，而在不太常见的变异中则表现为非遗忘性认知障碍。阿尔茨海默病是中年和晚年认知障碍的常见原因，但其临床影响会受到其他神经退行性和脑血管疾病的影响。本篇导论将阿尔茨海默病的生物学视为一种脑部疾病，其结果是突触稳态丧失与高度相互关联的内质体/溶酶体清除途径功能障碍之间复杂相互作用的结果，其中淀粉样β（Aβ）和tau蛋白的前体、聚集物及后转译修饰产物发挥着重要作用。尽管治疗努力仍在这一框架内挣扎以寻找实质性改变阿尔茨海默病患者临床进程的靶点。

英文摘要 ​

Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles. Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.

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主要研究问题 ​

  1. 阿尔茨海默病的遗传因素和环境因素如何相互作用影响疾病的发展？
  2. 除了β-淀粉样蛋白和tau蛋白，是否还有其他生物标志物可以用于早期诊断阿尔茨海默病？
  3. 阿尔茨海默病的不同临床表现如何与其他神经退行性疾病区分开来？
  4. 在阿尔茨海默病的治疗研究中，现阶段有哪些新兴的药物或疗法显示出希望？
  5. 阿尔茨海默病患者的生活质量如何受到其他伴随疾病的影响？

核心洞察 ​

研究背景和目的 ​

阿尔茨海默病（AD）是一种以β-淀粉样蛋白（Aβ）斑块和tau蛋白神经纤维缠结为特征的神经退行性疾病，主要导致认知功能障碍。该研究旨在深入探讨AD的病理生理机制、流行病学特征、诊断标准及其管理方法，强调AD与其他神经退行性疾病和脑血管疾病之间的复杂关系。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，系统回顾AD的流行病学、病理机制、临床表现、诊断和管理策略。研究通过对现有文献的分析，归纳了AD的主要生物标志物和治疗方法。

Mermaid diagram

关键结果和发现 ​

  1. 流行病学：AD是最常见的痴呆症，发病率随着年龄的增长而显著增加。预期到2050年，全球痴呆症患者将达到1.13亿。
  2. 病理机制：AD的主要病理特征包括Aβ斑块和tau蛋白缠结，二者在神经元功能障碍和死亡中起关键作用。
  3. 临床表现：AD患者常表现出明显的记忆障碍，此外还可能出现语言、视觉空间和执行功能的障碍。
  4. 诊断标准：通过临床评估和生物标志物（如Aβ和tau蛋白的PET成像和CSF分析）进行AD的诊断。
  5. 管理策略：目前AD的治疗主要包括药物干预（如胆碱酯酶抑制剂和NMDA受体拮抗剂）和非药物干预（如生活方式改变和认知训练）。

主要结论/意义/创新性 ​

AD是一种复杂的多因素疾病，涉及遗传、环境和生活方式等多种因素。通过理解AD的生物学机制和流行病学特征，可以为早期诊断和个性化治疗提供基础。研究强调了多种生物标志物在AD诊断和管理中的重要性，并呼吁未来的研究应集中于病理机制的进一步探索及新疗法的开发。

研究局限性和未来方向 ​

  1. 局限性：当前对AD的理解仍不够全面，尤其是在生物标志物的特异性和灵敏性方面。此外，许多临床试验结果的可重复性和普遍性尚待验证。
  2. 未来方向：未来的研究应聚焦于多种病理过程的交互作用、个体化治疗策略的开发以及早期预防措施的实施。进一步探索新型生物标志物和治疗方法，将有助于改善AD患者的生活质量。

参考文献 ​

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引用本文的文献 ​

  1. Identification of Multi-Target Anti-AD Chemical Constituents From Traditional Chinese Medicine Formulae by Integrating Virtual Screening and In Vitro Validation. - Baoyue Zhang;Jun Zhao;Zhe Wang;Pengfei Guo;Ailin Liu;Guanhua Du - Frontiers in pharmacology (2021)
  2. Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer's Disease. - Erika Kropf;Margaret Fahnestock - Cells (2021)
  3. Artificial Intelligence for Alzheimer's Disease: Promise or Challenge? - Carlo Fabrizio;Andrea Termine;Carlo Caltagirone;Giulia Sancesario - Diagnostics (Basel, Switzerland) (2021)
  4. A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline. - Rongcan Luo;Yu Fan;Jing Yang;Maosen Ye;Deng-Feng Zhang;Kun Guo;Xiao Li;Rui Bi;Min Xu;Lu-Xiu Yang;Yu Li;Xiaoqian Ran;Hong-Yan Jiang;Chen Zhang;Liwen Tan;Nengyin Sheng;Yong-Gang Yao - Signal transduction and targeted therapy (2021)
  5. First-in-Class Isonipecotamide-Based Thrombin and Cholinesterase Dual Inhibitors with Potential for Alzheimer Disease. - Rosa Purgatorio;Nicola Gambacorta;Modesto de Candia;Marco Catto;Mariagrazia Rullo;Leonardo Pisani;Orazio Nicolotti;Cosimo D Altomare - Molecules (Basel, Switzerland) (2021)
  6. Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer's Disease Treatment. - Saghar Rabiei Poor;Miren Ettcheto;Amanda Cano;Elena Sanchez-Lopez;Patricia Regina Manzine;Jordi Olloquequi;Antoni Camins;Mohammad Javan - Pharmaceuticals (Basel, Switzerland) (2021)
  7. Antidepressants in Alzheimer's Disease: A Focus on the Role of Mirtazapine. - Ana Salomé Correia;Nuno Vale - Pharmaceuticals (Basel, Switzerland) (2021)
  8. NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load. - Theresa Pohlkamp;Xunde Xian;Connie H Wong;Murat S Durakoglugil;Gordon Chandler Werthmann;Takaomi C Saido;Bret M Evers;Charles L White;Jade Connor;Robert E Hammer;Joachim Herz - eLife (2021)
  9. Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer's Disease. - Lushuang Xie;Yi Liu;Ning Zhang;Chenyu Li;Aaron F Sandhu;George Williams;Yan Shen;Hongying Li;Qiaofeng Wu;Shuguang Yu - Frontiers in neuroscience (2021)
  10. Magnolol upregulates CHRM1 to attenuate Amyloid-β-triggered neuronal injury through regulating the cAMP/PKA/CREB pathway. - Gemin Zhu;Yuan Fang;Xiaoli Cui;Ruihua Jia;Xiaogang Kang;Rui Zhao - Journal of natural medicines (2022)

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