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阿尔茨海默病的治疗:超越对症治疗。

Treatment of Alzheimer's Disease: Beyond Symptomatic Therapies.

机构信息

Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy.

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.

出版信息

Int J Mol Sci. 2023 Sep 9;24(18):13900. doi: 10.3390/ijms241813900.


DOI:10.3390/ijms241813900
PMID:37762203
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10531090/
Abstract

In an ever-increasing aged world, Alzheimer's disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of β-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against Aβ plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment.

摘要

在老龄化日益严重的世界中,阿尔茨海默病(AD)是痴呆症的首要病因,也是老年人常见的慢性疾病之一。世界卫生组织(WHO)估计,目前全球有 5500 万人受到该病影响,因此将 AD 视为具有公共优先级的疾病。遗憾的是,目前尚无针对该病的最终治愈方法。治疗策略旨在缓解症状,例如乙酰胆碱酯酶抑制剂(AChEI)和 N-甲基-D-天冬氨酸(NMDA)拮抗剂美金刚。目前,管理该病的最佳方法似乎是将药物治疗与非药物治疗相结合,以刺激认知储备。在过去的二十年中,已经发现了许多针对 AD 确立的生物学特征(β-淀粉样蛋白聚集体沉积和细胞内过度磷酸化 tau 蛋白的积累)的药物。尽管先前的努力令人失望,但最近 AD 的治疗已经进入了一个新时代。美国食品和药物管理局(FDA)于 2021 年有条件批准了第一种用于治疗 AD 的疾病修饰疗法(DMT)——针对 Aβ斑块和寡聚体的单克隆抗体 aducanumab,2023 年 1 月,FDA 加速批准了第二种单克隆抗体 lecanemab。本文描述了正在进行的 DMT 和非药物治疗的临床试验。我们还将根据新的生物标志物提出一个未来的设想,这些标志物可以在临床前或前驱期检测 AD,识别有患 AD 风险的人群,并允许早期进行治愈性治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d2/10531090/b8534b55e3d5/ijms-24-13900-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d2/10531090/b8534b55e3d5/ijms-24-13900-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d2/10531090/b8534b55e3d5/ijms-24-13900-g001.jpg

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本文引用的文献

[1]
Beyond dentistry: could prevention and screening for neurodegenerative diseases start in the dental office?

Neural Regen Res. 2024-1

[2]
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JAMA. 2023-8-8

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N Engl J Med. 2023-9-21

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Drug Dev Res. 2023-9

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Characterization of Pairs of Toxic and Nontoxic Misfolded Protein Oligomers Elucidates the Structural Determinants of Oligomer Toxicity in Protein Misfolding Diseases.

Acc Chem Res. 2023-6-20

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