Background Among plasma biomarkers for Alzheimer’s disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. Method pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well-characterised prospective multicentre BALTAZAR (Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk) cohort of participants with mild cognitive impairment (MCI). Results Among participants with MCI, 55% were Aβ+ and 29% developed dementia due to AD. pTau181 and pTau217 were higher in the Aβ+ population with fold change of 1.5 and 2.7, respectively. MCI that converted to AD also had higher levels than non-converters, with HRs of 1.38 (1.26 to 1.51) for pTau181 compared with 8.22 (5.45 to 12.39) for pTau217. The area under the curve for predicting Aβ+ was 0.783 (95% CI 0.721 to 0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95% CI 0.868 to 0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex and apolipoprotein E ε4 (APOEε4) status, in a logistic model. Age, APOEε4 and renal dysfunction were associated with pTau levels, but the clinical performance of pTau217 was only marginally altered by these factors. Using a two cut-point approach, a 95% positive predictive value for Aβ+ corresponded to pTau217 >0.8 pg/mL and a 95% negative predictive value at <0.23 pg/mL. At these two cut-points, the percentages of MCI conversion were 56.8% and 9.7%, respectively, while the annual rates of decline in Mini-Mental State Examination were −2.32 versus −0.65. Conclusions Plasma pTau217 and pTau181 both correlate with AD, but the fold change in pTau217 makes it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia. Data are available upon reasonable request. Data and informed consent form are available upon request after publication (APHP, Paris). Requests will be considered by each study investigator, based on the information provided by the requester, regarding the study and analysis plan. If the use is appropriate, a data sharing agreement will be put in place before distributing a fully deidentified version of the dataset, including the data dictionary used for analysis with individual participant data.

中文翻译：

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血浆 ALZpath pTau217 免疫分析评估轻度认知障碍的临床价值

背景 在阿尔茨海默病 (AD) 的血浆生物标志物中，pTau181 和 pTau217 是最有前途的。然而，从研究到常规临床使用的转变将需要在前瞻性队列中确认临床表现并评估共同因素。方法 在具有轻度认知障碍 (MCI) 的参与者的充分表征的前瞻性多中心 BALTAZAR（淀粉样蛋白肽和阿尔茨海默病风险的生物标志物）队列中，使用 Quanterix 和 ALZpath、SIMOA 测定对 pTau181 和 pTau217 进行定量。结果 在患有 MCI 的参与者中，55% 为 Aβ+，29% 因 AD 而发展为痴呆。 pTau181 和 pTau217 在 Aβ+ 群体中较高，倍数变化分别为 1.5 和 2.7。转化为 AD 的 MCI 也比未转化者具有更高的水平，pTau181 的 HR 为 1.38（1.26 至 1.51），而 pTau217 的 HR 为 8.22（5.45 至 12.39）。 pTau181 的预测 Aβ+ 的曲线下面积为 0.783（95% CI 0.721 至 0.836；切点 2.75 pg/mL），pTau217 的预测 Aβ+ 的曲线下面积为 0.914（95% CI 0.868 至 0.948；切点 0.44 pg/mL）。在逻辑模型中添加年龄、性别和载脂蛋白 E ε4 (APOEε4) 状态并不能提高 pTau217 的高预测能力。年龄、APOEε4 和肾功能障碍与 pTau 水平相关，但 pTau217 的临床表现仅受这些因素的轻微影响。使用两个切点方法，Aβ+ 的 95% 阳性预测值对应于 pTau217 >0.8 pg/mL，95% 的阴性预测值对应于 <0.23 pg/mL。在这两个分界点，MCI 转换的百分比分别为 56.8% 和 9.7%，而简易精神状态检查的年下降率分别为 -2.32 和 -0.65。结论 血浆pTau217和pTau181均与AD相关，但pTau217倍数变化可以更好地诊断脑淀粉样变性，并预测认知能力下降和转变为AD痴呆。数据可根据合理要求提供。数据和知情同意书可在出版后根据要求提供（APHP，巴黎）。每位研究研究者将根据请求者提供的有关研究和分析计划的信息来考虑请求。如果使用适当，将在分发完全去识别化的数据集版本之前制定数据共享协议，包括用于分析个体参与者数据的数据字典。