With the potential development of new disease-modifying Alzheimer’s disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by ¹⁸F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.

随着新的缓解阿尔茨海默氏病（AD）疗法的潜在发展，需要简单、广泛使用的筛查测试来识别哪些正在经历认知或行为下降症状的个体，应该进一步评估以开始治疗。与目前批准的脑脊液或淀粉样蛋白 β 正电子发射断层扫描 (PET) 诊断测试相比，基于血液的 AD 测试将是一种侵入性更小、成本更低的筛查工具。我们检查了血浆 tau 残基 181 (pTau181) 磷酸化是否可以区分临床诊断或尸检证实的 AD 和额颞叶变性。与对照组相比，AD 患者的血浆 pTau181 浓度增加了 3.5 倍，并且可以将 AD 与临床诊断的 AD（接受者操作特征曲线下面积为 0.894）和尸检确认的额颞叶变性（曲线下面积为 0.878）区分开来。无论临床诊断如何，血浆 pTau181 都能识别出 β-淀粉样蛋白 PET 阳性的个体，并且与¹⁸ F-flortaucipir PET 测量的皮质 tau 蛋白沉积相关。血浆 pTau181 可用于筛查与 AD 相关的 tau 病理。