Alzheimer's Disease and Brain Health, Eisai Inc., Nutley, NJ, USA.
Chambers-Grundy Center for Transformative Neuroscience, Pam Quirk Brain Health and Biomarker Laboratory, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, NV, USA.
Neuron. 2023 Sep 20;111(18):2781-2799. doi: 10.1016/j.neuron.2023.05.017. Epub 2023 Jun 8.
Timely detection of the pathophysiological changes and cognitive impairment caused by Alzheimer's disease (AD) is increasingly pressing because of the advent of biomarker-guided targeted therapies that may be most effective when provided early in the disease. Currently, diagnosis and management of early AD are largely guided by clinical symptoms. FDA-approved neuroimaging and cerebrospinal fluid biomarkers can aid detection and diagnosis, but the clinical implementation of these testing modalities is limited because of availability, cost, and perceived invasiveness. Blood-based biomarkers (BBBMs) may enable earlier and faster diagnoses as well as aid in risk assessment, early detection, prognosis, and management. Herein, we review data on BBBMs that are closest to clinical implementation, particularly those based on measures of amyloid-β peptides and phosphorylated tau species. We discuss key parameters and considerations for the development and potential deployment of these BBBMs under different contexts of use and highlight challenges at the methodological, clinical, and regulatory levels.
及时发现阿尔茨海默病(AD)引起的病理生理变化和认知障碍变得越来越紧迫,因为基于生物标志物的靶向治疗的出现可能在疾病早期最为有效。目前,AD 的早期诊断和管理主要依赖于临床症状。获得 FDA 批准的神经影像学和脑脊液生物标志物可辅助检测和诊断,但由于可用性、成本和被认为具有侵入性,这些检测方式的临床应用受到限制。基于血液的生物标志物 (BBBMs) 可能实现更早更快的诊断,并有助于风险评估、早期发现、预后和管理。在此,我们回顾了最接近临床应用的 BBBMs 数据,特别是基于淀粉样蛋白-β肽和磷酸化 tau 物质测量的 BBBMs。我们讨论了在不同使用情况下开发和潜在部署这些 BBBMs 的关键参数和考虑因素,并强调了在方法学、临床和监管层面上的挑战。