Yu Lei, Wang Tianhao, Hansson Oskar, Janelidze Shorena, Lamar Melissa, Arfanakis Konstantinos, Bennett David A, Schneider Julie A, Boyle Patricia A
Rush Alzheimer's Disease Center (LY, TW, ML, KA, DAB, JAS, PAB), Rush University Medical Center, Chicago, IL; and Clinical Memory Research Unit (OH, SJ), Department of Clinical Sciences, Lund University, Malmö, Sweden.
Neurol Clin Pract. 2024 Jun;14(3):e200291. doi: 10.1212/CPJ.0000000000200291. Epub 2024 Apr 15.
Structural brain MRI and blood-based phosphorylated tau (p-tau) measures are among the least invasive and least expensive Alzheimer's disease (AD) biomarkers to date. The extent to which these biomarkers may outperform one another in predicting future Alzheimer dementia diagnosis is poorly understood, however. This study investigated 2 specific AD biomarkers, i.e., a cortical thickness signature of AD (AD-CT) and plasma p-tau217, for predicting Alzheimer dementia.
Data came from community-dwelling older participants of the Religious Orders Study or the Rush Memory and Aging Project. AD-CT was obtained from 3T MRI scans using a magnetization-prepared rapid acquisition gradient echo sequence and by averaging thickness from previously identified cortical regions implicated in AD. Plasma p-tau217 was quantified using an immunoassay developed by Lilly Research Laboratories on the MSD platform. Both MRI scans and blood specimens were collected at the same visits, and subsequent diagnoses of Alzheimer dementia were determined through annual detailed clinical evaluations. Cox proportional hazards models examined the associations of the 2 biomarkers with incident Alzheimer dementia, and prediction accuracy was assessed using c-statistics.
A total of 198 older adults, on average 84 years of age, were included. Over a mean follow-up of 4 years, 60 (30%) individuals developed Alzheimer dementia. AD-CT (hazard ratio: 1.71, 95% CI 1.26-2.31) and separately plasma p-tau217 (hazard ratio: 2.57, 95% CI 1.83-3.61) were associated with incident Alzheimer dementia. The c-statistic for prediction accuracy was consistently higher for plasma p-tau217 (between 0.74 and 0.81) than AD-CT (between 0.70 and 0.75) across a range of time horizons. Furthermore, with both biomarkers included in the same model, there was only modest improvement in the c-statistic due to AD-CT.
Plasma p-tau217 outperforms an imaging-based cortical thickness signature of AD in predicting future Alzheimer dementia diagnosis. Furthermore, the AD cortical thickness signature adds little to the prediction accuracy above and beyond plasma p-tau217.
结构性脑磁共振成像（MRI）和基于血液的磷酸化tau蛋白（p-tau）检测是迄今为止侵入性最小且成本最低的阿尔茨海默病（AD）生物标志物。然而，目前对于这些生物标志物在预测未来阿尔茨海默痴呆症诊断方面的表现优劣程度尚知之甚少。本研究调查了两种特定的AD生物标志物，即AD的皮质厚度特征（AD-CT）和血浆p-tau217，用于预测阿尔茨海默痴呆症。
数据来自宗教团体研究或拉什记忆与衰老项目中居住在社区的老年参与者。AD-CT通过使用磁化准备快速采集梯度回波序列的3T MRI扫描获得，并通过平均先前确定的与AD相关的皮质区域的厚度来获取。血浆p-tau217使用礼来研究实验室在MSD平台上开发的免疫测定法进行定量。MRI扫描和血液样本均在同一次就诊时采集，随后通过年度详细临床评估确定阿尔茨海默痴呆症的诊断。Cox比例风险模型检验了这两种生物标志物与阿尔茨海默痴呆症发病的关联，并使用c统计量评估预测准确性。
共纳入198名平均年龄为84岁的老年人。在平均4年的随访期间，60名（30%）个体患上了阿尔茨海默痴呆症。AD-CT（风险比：1.71，95%置信区间1.26 - 2.31）以及血浆p-tau217（风险比：2.57，95%置信区间1.83 - 3.61）均与阿尔茨海默痴呆症发病相关。在一系列时间范围内，血浆p-tau217的预测准确性c统计量（在0.74至0.81之间）始终高于AD-CT（在0.70至0.75之间）。此外，当两种生物标志物纳入同一模型时，由于AD-CT，c统计量仅有适度改善。
在预测未来阿尔茨海默痴呆症诊断方面，血浆p-tau217的表现优于基于成像的AD皮质厚度特征。此外，AD皮质厚度特征在预测准确性方面，相较于血浆p-tau217并没有显著提升。
