APN-1808

A new blood test called p-tau217 shows promise as an Alzheimer's disease biomarker, and when used in a two-step workflow very high accuracy to either identify or exclude brain amyloidosis, the most important and earliest pathology. A new blood test called p-tau217 shows promise as an Alzheimer's disease biomarker, and when used in a two-step workflow very high accuracy to either identify or exclude brain amyloidosis, the most important and earliest pathology. That is an innovation now presented by researchers at the University of Gothenburg, together with colleagues at University of Lund and in Montreal, Canada. In recent years, a lot of effort has been put on developing biomarkers in blood that could potentially help to identify Alzheimer's disease (AD). Tau protein, in particular its phosphorylated variant (p-tau) -- and one of the main proteins involved in AD pathology -- has been the focus of extensive research and developments the last years. The new blood-based p-tau biomarkers, especially a variant called p-tau217, have shown great promise as clinically useful tools to screen patients with memory problems or other early cognitive symptoms suggestive of early Alzheimer's disease. However, even if promising, a concern has been that classifying early patients into either having "AD or not AD" will still result in a rather high percentage of false positives (individuals with a positive test result who do not have AD) and false negatives (individuals with a negative test result who prove to have AD based on other examinations such as amyloid PET scans). Considering not only ethical and psychological concerns induced by possible misdiagnosis, but also high costs and potential medical risks of initiating treatments on people not having the target disease), the scientists at the University of Gothenburg and their colleagues developed a novel strategy for the clinical implementation of blood biomarkers. Two-step workflow The two-step model is built on a first step with a diagnostic model (based on plasma p-tau217 together with age and APOE e4) to stratify patients with mild cognitive impairment (MCI) for risk of amyloid PET positivity. Step 2 is based on confirmatory testing with CSF Ab42/40 ratio (or amyloid EPT) only in those with uncertain outcomes in step 1. The workflow was evaluated in 348 MCI participants from the Swedish BioFINDER studies (Lund University) and validated in the independent TRIAD cohort (McGill University, Montreal, Canada) also using an independent method for analysis of plasma p-tau217. Very high accuracy The model was evaluated at three different thresholding strategies were explored to classify participants into groups with low, intermediate and high risk for being "Aβ positive" (having AD-type pathology). At the stringent lower probability thresholds with 97.5% sensitivity (to avoid missing detection of patients who are Aβ positive), as little as 6.6% false negatives was found, while the stringent 97.5% specificity (to avoid classifying patients who are Aβ negative as 'high risk') gave only 2.3% false positives. At the stringent sensitivity/specificity thresholds, 41% of patients fell into the intermediate risk group (compared to 29% of patients for the 95% thresholds). Further evaluations of this group with CSF Aβ42/40 showed very good agreement (86%) with amyloid PET results. Results were verified in the independent McGill cohort of patients. A clinically useful strategy for p-tau217 blood test for AD screening The study presents a blood plasma p-tau217-based two-step model for risk stratification of patients with MCI into high, low- and intermediate-risk of having brain amyloidosis and early AD pathology. The blood test applied in step 1 shows very high accuracy to identify high-risk patients, who depending on the clinical situation can either be given a diagnosis and be initiated on symptomatic treatments, or in the future be referred to the specialist clinic for possible initiation disease-modifying treatment. In the low-risk group, AD can be excluded with high degree of certainty. The intermediate risk group will only encompass around one third of patients, which substantially will reduce the need for confirmatory CSF or PET testing at the specialist clinic, and thus cost savings for the society.

▎药明康德内容团队编辑阿尔茨海默病是老年人中最常见的神经退行性疾病。近两年来阿尔茨海默病的治疗不断获得突破，FDA已经批准了两款新疗法。不过，由于缺少精准的诊断工具，对于初级保健医生（primary care doctors）来说，准确诊断阿尔茨海默病仍然十分困难。今日在阿尔茨海默病协会国际会议（AAIC）上发表的最新研究显示，一款只需要从指尖取血的血液检测可能帮助患者在家中或当地诊所发现阿尔茨海默病。瑞典哥德堡大学（University of Gothenburg）的研究团队开发了一种指尖取血的检测手段，用于测量和阿尔茨海默病相关的关键生物标志物，包括神经丝蛋白（NfL）、胶质纤维酸性蛋白（GFAP）和磷酸化tau蛋白（p-tau181和217）。他们从巴塞罗那ACE阿尔茨海默病中心的77名记忆门诊患者中采集了血液（静脉取血和手指取血）。将血样转移至干血斑卡上，并在不进行温度控制或冷却的情况下连夜运输至瑞典哥德堡大学。在那里，从卡片中提取干血样，测定NfL、GFAP和p-tau181和217。在静脉取血获得的血斑中，GFAP、NfL、p-tau217和p-tau181的水平与标准血液分析密切相关。从手指采血中提取的GFAP、NfL和p-tau217也与标准采血方式高度相关。图片来源：123RF研究人员表示，这一初步研究证明了在没有低温储存或特别制备或处理的情况下，远程收集和测量阿尔茨海默病生物标志物的潜力。目前，阿尔茨海默病血液测试的使用受限于需要到诊所就诊、由经过培训的人员给药以及严格的时间限制和依赖低温的交付和储存程序。一种允许在家中采血的方法，简单到可以独立进行，或由护理人员进行，将增加这些检测的可及性。这将改善早期诊断，并更好地监测被认为“有风险”或正在接受获批治疗的患者。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Simple Finger Prick Test Exemplifies Advances in Alzheimer’s Disease Blood Tests. Retrieved July 19, 2023, from https://aaic.alz.org/releases_2023/finger-prick-blood-test-alzheimers-disease.asp免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新