Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital The Thai Red Cross Society, Bangkok, Thailand.
Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Alzheimers Dement. 2024 Sep;20(9):6456-6467. doi: 10.1002/alz.14138. Epub 2024 Jul 17.
Plasma phosphorylated tau (p-tau)217 is a promising biomarker for Alzheimer's disease (AD) diagnosis, but its clinical implementation remains challenging. We propose a strategy based on Bayes' theorem and test it in real-life memory clinics.
Memory clinic patients were evaluated by neurocognitive specialists for prespecified diagnosis and subsequently underwent blood collection for p-tau217, cerebrospinal fluid, or amyloid positron emission tomography. Using cross-validation, the Bayesian approach (pretest probability × individualized likelihood ratio) was compared to other models for AD diagnosis.
The Bayesian strategy demonstrated an area under the receiver operating characteristic curve (AUC) of 0.98 (95% confidence interval [CI]: 0.96-1.0), significantly outperforming multivariable logistic regression (p-tau217, age, apolipoprotein E; AUC 0.95, p = 0.024) and p-tau217 alone (AUC = 0.94, p = 0.007). When applying the two-threshold approach, the Bayesian strategy yielded an accuracy of 0.94 (95% CI: 0.88-1.0) without requiring confirmatory tests in 62.9% of the iterations.
The Bayesian strategy offers an effective and flexible approach to address the limitations of plasma p-tau217 in clinical practice.
Incorporating pretest probability into the interpretation of plasma phosphorylated tau (p-tau)217 improves the diagnostic performance significantly. The strategy could obviate the need for confirmatory testing in most of the patients. Plasma p-tau217 proves useful as a biomarker for Alzheimer's disease in low- and middle-income country such as Thailand.
血浆磷酸化 tau（p-tau）217 是阿尔茨海默病（AD）诊断的有前途的生物标志物，但其实用性仍然具有挑战性。我们提出了一种基于贝叶斯定理的策略，并在实际的记忆诊所中进行了测试。
神经认知专家根据预设的诊断标准对记忆诊所的患者进行评估，然后采集血液样本用于检测 p-tau217、脑脊液或淀粉样蛋白正电子发射断层扫描。通过交叉验证，将贝叶斯方法（先验概率×个体化似然比）与 AD 诊断的其他模型进行比较。
贝叶斯策略的受试者工作特征曲线下面积（AUC）为 0.98（95%置信区间[CI]：0.96-1.0），明显优于多变量逻辑回归（p-tau217、年龄、载脂蛋白 E；AUC 0.95，p=0.024）和单独的 p-tau217（AUC=0.94，p=0.007）。当应用双阈值方法时，该策略在 62.9%的迭代中无需进行确认性测试即可达到 0.94（95%CI：0.88-1.0）的准确率。
贝叶斯策略为解决血浆 p-tau217 在临床实践中的局限性提供了一种有效且灵活的方法。
将先验概率纳入对血浆磷酸化 tau（p-tau）217 的解释中可显著提高诊断性能。该策略可避免大多数患者进行确认性检测。血浆 p-tau217 可作为一种有用的生物标志物，用于在像泰国这样的中低收入国家进行阿尔茨海默病的诊断。
