Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes.
Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes.
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DOI：
10.3233/jad-230694
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发表时间：
2023
影响因子：
4
通讯作者：
Schmidt, Harald H. H. W.
中科院分区：
文献类型：
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作者：
Pachado, Mayra Pacheco;Casas, Ana I.;Elbatreek, Mahmoud H.;Nogales, Cristian;Guney, Emre;Espay, Alberto J.;Schmidt, Harald H. H. W.
关键词：
阿尔茨海默氏病（AD）和其他形式的痴呆症一起是全球老龄化人口中残疾和死亡的主要原因，给个人、社会和经济带来沉重负担。它们也是药物开发失败的最突出的例子之一。事实上，在40多项抗淀粉样蛋白干预的AD试验之后，淀粉样蛋白-β（Aβ）的减少从未转化为临床相关的益处，并且在一些情况下产生了危害。根本的问题是一个世纪以来，以大脑为中心的疾病定义忽视了因果机制和合并症。在这篇假设文章中，我们讨论了这种当前过时的痴呆病理学如何成为精准医学的关键障碍，并阐明了网络医学如何用分子内型取代临床病理表型，并提出了一个新的框架，以实现神经退行性疾病患者的精准和治愈性药物。
Alzheimer’s disease (AD) and other forms of dementia are together a leading cause of disability and death in the aging global population, imposing a high personal, societal, and economic burden. They are also among the most prominent examples of failed drug developments. Indeed, after more than 40 AD trials of anti-amyloid interventions, reduction of amyloid-β (Aβ) has never translated into clinically relevant benefits, and in several cases yielded harm. The fundamental problem is the century-old, brain-centric phenotype-based definitions of diseases that ignore causal mechanisms and comorbidities. In this hypothesis article, we discuss how such current outdated nosology of dementia is a key roadblock to precision medicine and articulate how Network Medicine enables the substitution of clinicopathologic phenotypes with molecular endotypes and propose a new framework to achieve precision and curative medicine for patients with neurodegenerative disorders.