Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Nat Med. 2023 Sep;29(9):2187-2199. doi: 10.1038/s41591-023-02505-2. Epub 2023 Sep 4.
Alzheimer disease (AD) is the most common contributor to dementia in the world, but strategies that slow or prevent its clinical progression have largely remained elusive, until recently. This Review highlights the latest advances in biomarker technologies and therapeutic development to improve AD diagnosis and treatment. We review recent results that enable pathological staging of AD with neuroimaging and fluid-based biomarkers, with a particular emphasis on the role of amyloid, tau and neuroinflammation in disease pathogenesis. We discuss the lessons learned from randomized controlled trials, including some supporting the proposal that certain anti-amyloid antibodies slow cognitive decline during the mildly symptomatic phase of AD. In addition, we highlight evidence for newly identified therapeutic targets that may be able to modify AD pathogenesis and progression. Collectively, these recent discoveries-and the research directions that they open-have the potential to move AD clinical care toward disease-modifying treatment strategies with maximal benefits for patients.
阿尔茨海默病(AD)是全球导致痴呆的最常见原因,但直到最近,仍缺乏能延缓或预防其临床进展的策略。这篇综述强调了生物标志物技术和治疗开发方面的最新进展,以改善 AD 的诊断和治疗。我们回顾了最近的研究结果,这些结果使得可以通过神经影像学和基于流体的生物标志物进行 AD 的病理分期,特别强调了淀粉样蛋白、tau 和神经炎症在疾病发病机制中的作用。我们讨论了从随机对照试验中吸取的经验教训,包括一些支持某些抗淀粉样蛋白抗体在 AD 的轻度症状阶段能减缓认知能力下降的建议。此外,我们还强调了新发现的治疗靶点的证据,这些靶点可能能够改变 AD 的发病机制和进展。总的来说,这些最近的发现及其开辟的研究方向有可能使 AD 的临床护理转向具有最大患者获益的疾病修饰治疗策略。