Schöll M, Vrillon A, Ikeuchi T, Quevenco F C, Iaccarino L, Vasileva-Metodiev S Z, Burnham S C, Hendrix J, Epelbaum S, Zetterberg H, Palmqvist S
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK; Department of Neuropsychiatry, Sahlgrenska University Hospital, Mölndal, Sweden.
French Institute of Health and Medical Research (Inserm), Paris, France.
J Prev Alzheimers Dis. 2025 Apr;12(4):100056. doi: 10.1016/j.tjpad.2024.100056. Epub 2025 Jan 14.
As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic. We focus on plasma phosphorylated(p)-tau, specifically plasma p-tau217, as a robust candidate across both primary and secondary care settings. Despite the high performance and robustness demonstrated in research, plasma p-tau217, like all plasma biomarkers, can be affected by analytical and pre-analytical variability as well as patient comorbidities, sex, ethnicity, and race. This review also discusses the advantages of the two-point cut-off approach to mitigating these factors, and the challenges raised by the resulting intermediate range measurements, where clinical guidance is still unclear. Further validation of plasma p-tau217 in heterogeneous, real-world cohorts will help to increase confidence in testing and support establishing a standardized approach. Plasma biomarkers are poised to become a more affordable and less invasive alternative to PET and CSF testing. However, understanding the factors that impact plasma biomarker measurement and interpretation is critical prior to their implementation in routine clinical use.
随着新型抗淀粉样蛋白疗法的应用越来越广泛，及时准确的诊断对于确保早期阿尔茨海默病（AD）患者获得最佳治疗至关重要。血浆生物标志物是识别AD病理的一种有前景的工具；然而，在将其应用于常规临床之前，需要考虑几个技术和临床因素。鉴于该领域的快速发展以及可用生物标志物和检测方法的多样性，本综述旨在总结这些注意事项，评估现有平台，并讨论将血浆生物标志物检测引入临床所需的步骤。我们重点关注血浆磷酸化（p）-tau，特别是血浆p-tau217，它是初级和二级护理环境中强有力的候选指标。尽管在研究中已证明血浆p-tau217具有高性能和稳健性，但与所有血浆生物标志物一样，它会受到分析和分析前变异性以及患者合并症、性别、种族和民族的影响。本综述还讨论了采用两点截断法减轻这些因素的优势，以及由此产生的中间范围测量所带来的挑战，目前临床指导仍不明确。在异质性的真实世界队列中对血浆p-tau217进行进一步验证，将有助于提高检测的可信度，并支持建立标准化方法。血浆生物标志物有望成为正电子发射断层扫描（PET）和脑脊液检测更经济、侵入性更小的替代方法。然而，在将其应用于常规临床之前，了解影响血浆生物标志物测量和解释的因素至关重要。
