Perspective: Minimally clinically important “symptomatic” benefit associated with disease modification resulting from anti-amyloid immunotherapy

John Alam, Marwan N. Sabbagh
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引用次数: 0

Abstract

Despite some skepticism regarding the amyloid hypothesis, there is growing evidence that clearing amyloid by targeting specific species of amyloid (plaque, oligomers, fibrils, and protofibrils) for removal has therapeutic benefits. Specifically, there is growing evidence that, in mild cognitive impairment and mild dementia due to Alzheimer's disease (AD), robust and aggressive removal of amyloid can slow cognitive decline as measured by global instruments, composite measures, and cognitive testing. Furthermore, clinical efficacy signals coupled with clear biomarker changes provide the first evidence of disease modification. This effect seems to be in addition to symptomatic treatments and opens speculation that the effect of anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration that is a result of disease modification.

Highlights

  • Clearance of brain amyloid plaques may lead to a clinical benefit in patients with early AD.
  • Aggregated Aβ may play a role in both disease expression and progression.
  • Anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration resulting from disease modification.
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观点:抗淀粉样蛋白免疫治疗与疾病改善相关的最低临床重要“症状性”获益。
尽管一些人对淀粉样蛋白假说持怀疑态度,但越来越多的证据表明,通过针对特定种类的淀粉样蛋白(斑块、低聚物、原纤维和原纤维)清除淀粉样蛋白具有治疗益处。具体来说,越来越多的证据表明,在阿尔茨海默病(AD)引起的轻度认知障碍和轻度痴呆中,通过全球仪器、综合测量和认知测试,强有力和积极地去除淀粉样蛋白可以减缓认知衰退。此外,临床疗效信号加上明确的生物标志物变化提供了疾病改变的第一个证据。这种效果似乎是对症治疗的补充,并开启了一种推测,即抗淀粉样蛋白单克隆抗体的作用可能通过疾病改变导致的症状改善而具有临床意义。重点:清除脑淀粉样斑块可能对早期AD患者有临床益处。聚集的a β可能在疾病表达和进展中发挥作用。抗淀粉样蛋白单克隆抗体可能通过疾病修饰引起的症状改善而具有临床意义。
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来源期刊
CiteScore
10.10
自引率
2.10%
发文量
134
审稿时长
10 weeks
期刊介绍: Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.
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