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INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: The Bayesian strategy offers an effective and flexible approach to address the limitations of plasma p-tau217 in clinical practice. HIGHLIGHTS: 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.
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INTRODUCTION: Despite the substantial accuracy of plasma p-tau in diagnosing Alzheimer's disease (AD) in research cohorts, data on real-life memory clinic patients are lacking. METHODS: Memory clinic patients at their early symptomatic stages were prospectively enrolled to undergo routine clinical assessment, plasma p-tau181 quantification (Simoa), amyloid and tau-positron emission tomography (PET). The diagnostic performance of plasma p-tau181, neurocognitive specialists, and regional tau-PET were compared head-to-head using amyloid-PET as the reference standard. RESULTS: Plasma p-tau181 has the area under the curve (AUC), sensitivity, specificity, and accuracy of 0.84 (95% confidence interval [CI] 0.73-0.94), 0.80 (95% CI 0.64-0.90), 0.75 (95% CI 0.51-0.90), and 0.78 (95% CI 0.65-0.88) for detecting amyloid-PET positivity in early symptomatic patients, respectively. The AUC of clinical diagnosis and tau-PET were 0.70 (95% CI 0.56-0.85) and 0.88 (95% CI 0.79-0.97), respectively. DISCUSSION: Plasma p-tau181 also performed well in real-life memory clinic settings and its role in clinical practice is supported.
