Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease

Linda J. Van Eldik, Eric R. Siemers, Emily C. Collins, Michael Gold, David Henley, Peter Johannsen, Hans J. Möbius, Melanie Shulman, Jin Zhou, Maria Carrillo, Christopher Weber
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Abstract

The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13–14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs. Participants also discussed the current definition of therapies that target underlying AD pathophysiology, what endpoints best define what is considered a meaningful change beyond the current approved definition for clinical efficacy, and how the recent NANT findings should inform the development of future guidelines for AD classification and personalized treatment strategies.

Highlights

  • The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government to review the current state of non-beta amyloid and non-tau (NANT) targets on underlying Alzheimer's disease (AD) pathophysiology.
  • The totality of scientific and clinical evidence supports the hypothesis that emerging NANT targets play a role in cognitive decline and neurodegeneration in AD.
  • New biomarkers based on NANT targets must be globally developed and implemented with specific consideration of fluid biomarkers as a cost-effective clinical option, to ensure better, more equitable treatment options for AD.
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了解阿尔茨海默病非淀粉样蛋白/非陶氏体 (NANT) 生物标记物和治疗靶点的最新进展
阿尔茨海默病(AD)研究界在拓展早期检测和治疗方法方面继续取得长足进步,其中包括我们最近在了解经典靶点(β-淀粉样蛋白和tau)之外的阿尔茨海默病基本病理生理学方面取得的进展。最近的临床试验结果表明,多种非淀粉样蛋白/非 tau(NANT)方法有望减缓阿兹海默症患者的认知能力衰退。阿尔茨海默氏症协会研究圆桌会议(AARR)于 2022 年 12 月 13-14 日举行,会议回顾了非淀粉样蛋白/非 tau(NANT)靶点在阿尔茨海默氏症病理生理学基础上的现状及其对认知能力下降的作用、各种非淀粉样蛋白/非 tau 生物标志物和治疗靶点的当前数据,以及将非淀粉样蛋白/非 tau 概念纳入临床试验设计的情况。与会者还讨论了针对阿兹海默病潜在病理生理学的疗法的当前定义、什么终点最能定义超出当前批准的临床疗效定义的有意义改变,以及最近的 NANT 研究结果应如何为未来阿兹海默病分类和个性化治疗策略指南的制定提供参考。 亮点阿尔茨海默病协会研究圆桌会议(AARR)召集了来自业界、学术界和政府的领导者,共同回顾了非β淀粉样蛋白和非tau(NANT)靶点对阿尔茨海默病(AD)病理生理学的影响现状。 所有的科学和临床证据都支持这样一个假设,即新出现的 NANT 靶点在阿尔茨海默病的认知功能衰退和神经变性中发挥着作用。 必须在全球范围内开发和实施基于 NANT 靶点的新生物标记物,并将流体生物标记物作为一种具有成本效益的临床选择加以具体考虑,以确保为阿尔茨海默病提供更好、更公平的治疗选择。
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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.
期刊最新文献
Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists Predicting regional tau accumulation with machine learning-based tau-PET and advanced radiomics Site-level factors affecting nursing home implementation of a personalized music intervention: Qualitative analyses from Music & Memory: A Pragmatic Trial for Nursing Home Residents with Alzheimer's Disease (METRIcAL) The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in APOE ε4 non-carriers with mild cognitive impairment due to Alzheimer's disease
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