The Immunopathy of Alzheimer's Disease: Innate or Adaptive?

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Current Alzheimer research Pub Date : 2023-01-01 DOI:10.2174/1567205020666230517103312
Donald F Weaver
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Abstract

Beyond the time-honoured targeting of protein misfolding and aggregation, Alzheimer's disease needs new, innovative therapeutic directions. When exploring alternative druggable mechanisms, multifaceted in vitro and in vivo data demonstrate that immune system dysfunction is a pivotal driver of Alzheimer's disease progression. In pursuing neuroimmunological targets, a major but often under-discussed consideration regards the issue of whether innate or adaptive immunity (or both) within the neuroimmune network should be the centre of focus when devising immunotherapeutic approaches to Alzheimer's. This perspective article briefly reviews current data, concluding that while both innate and adaptive immunity contributes to the immunopathology of Alzheimer's, the proinflammatory microglia and cytokines of innate immunity will provide higher yield targets with a greater likelihood of efficacy. Although it seems paradoxical to focus on a rapid, short-lived aspect of immunity when seeking approaches to a quintessentially chronic brain disease, accumulating evidence affords ample data to support the target-rich cascade of innate immunity for the development of much-needed new diagnostics and therapeutics.

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阿尔茨海默病的免疫病变:先天的还是适应性的?
除了长期以来针对蛋白质错误折叠和聚集的靶向治疗之外,阿尔茨海默病还需要新的、创新的治疗方向。在探索其他可药物机制时,多方面的体外和体内数据表明,免疫系统功能障碍是阿尔茨海默病进展的关键驱动因素。在追求神经免疫靶点的过程中,在设计阿尔茨海默氏症的免疫治疗方法时,神经免疫网络中的先天免疫或适应性免疫(或两者兼而有之)是否应该成为关注的焦点,这是一个主要但经常被忽视的问题。这篇前瞻性的文章简要回顾了目前的数据,得出结论,虽然先天免疫和适应性免疫都有助于阿尔茨海默氏症的免疫病理,但先天免疫的促炎小胶质细胞和细胞因子将提供更高的产量靶点,更有可能有效。虽然在寻找治疗典型慢性脑部疾病的方法时,专注于免疫的快速、短期方面似乎是自相矛盾的,但积累的证据提供了充足的数据来支持先天免疫的丰富靶标级联,以开发急需的新诊断和治疗方法。
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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
期刊介绍: Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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