本文由小咖机器人翻译整理

期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02869-z

摘要内容如下：

随着阿尔茨海默病（AD）疾病改善疗法的出现，确定哪些患者可以从这些治疗中获益变得至关重要。我们评估了在检测β淀粉样蛋白（Aβ）斑块和tau蛋白缠结时，精确的血液检测是否能像已建立的脑脊液（CSF）检测一样有效。在瑞典Biofinder-2队列（n=1，422）和美国Knight ADRC队列（n=337）中，通过质谱法分析血浆%p-Tau217（磷酸化Tau217与非磷酸化Tau的比率）。用临床使用和FDA批准的Aβ42/40和p-Tau181/Aβ42自动免疫测定法分析匹配的CSF样本。主要和次要结果分别是使用PET成像作为参考标准检测脑Aβ或Tau病理。主要分析集中于认知障碍患者（轻度认知障碍和轻度痴呆），这是可用的疾病改善治疗的目标人群。血浆%p-Tau217在临床上等同于FDA批准的AβPET状态分类的CSF测试，两者的曲线下面积（AUC）均在0.95-0.97之间。在AUC为0.95-0.98的Tau-PET分类中，血浆%p-Tau217通常优于CSF测试。在认知障碍亚组中（Biofinder-2:n=720；Knight ADRC：n=50），血浆%p-Tau217对AβPET的准确性、阳性预测值和阴性预测值为89-90%，对Tau-PET状态的准确性、阳性预测值和阴性预测值为87-88%，这在临床上与CSF测试相当，使用两种截断法进一步提高到95%。血浆%P-Tau217在AD病理学检测中的临床表现相当于或优于临床使用的FDA批准的CSF测试。在临床实践中使用高性能血液检测可以提高准确AD诊断和AD特异性治疗的可及性。

英文原文如下：

Abstracts

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using PET imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area-under-the-curve (AUC) for both between 0.95-0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired sub-cohorts (BioFINDER-2: n=720; Knight ADRC: n=50), plasma %p-tau217 had an accuracy, positive predictive value and negative predictive value of 89-90% for Aβ PET and 87-88% for tau-PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two cut-off approach. Blood plasma %p-tau217 demonstrated performance clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.

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