Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer’s disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87–0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94–0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials.

血浆磷酸化 tau181 (P-tau181) 可能在阿尔茨海默病 (AD) 中增加，但其对鉴别诊断和预后的有用性尚不清楚。我们在三个队列中研究了血浆 P-tau181，共有 589 人，包括认知未受损的参与者和患有轻度认知障碍 (MCI)、AD 痴呆和非 AD 神经退行性疾病的患者。血浆 P-tau181 在临床前 AD 中增加，并在 MCI 和痴呆阶段进一步增加。它与 CSF P-tau181 相关，并预测阳性 Tau 正电子发射断层扫描 (PET) 扫描（不同脑区的曲线下面积 (AUC) = 0.87-0.91）。血浆 P-tau181 区分 AD 痴呆与非 AD 神经退行性疾病的准确度与 Tau PET 和 CSF P-tau181 相似（AUC = 0.94-0.98），并在尸检确认的队列中检测到 AD 神经病理学。高血浆 P-tau181 与认知未受损和 MCI 受试者随后发展为 AD 痴呆有关。总之，血浆 P-tau181 是 AD 的非侵入性诊断和预后生物标志物，可能在临床实践和试验中有用。