Hazan Jemma, Abel Emily, Rosa Grilo Miguel, Alawode Deborah, Laranjinha Ines, Heslegrave Amanda J, Liu Kathy Y, Schott Jonathan M, Howard Robert, Zetterberg Henrik, Fox Nick C
Division of Psychiatry, UCL, London, UK
UCL, UK Dementia Research Institute, London, UK.
J Neurol Neurosurg Psychiatry. 2025 May 14;96(6):566-572. doi: 10.1136/jnnp-2024-334122.
Can plasma biomarkers as well as cerebrospinal fluid (CSF) perform in the separation of amyloid-beta-positive (Aβ+) vs amyloid-beta-negative (Aβ-) groups across an age range seen in an NHS cognitive disorder clinic?
As part of the routine diagnostic investigation of 111 clinic patients who had contemporaneous blood and CSF samples taken, patients were categorised into Aβ+ and Aβ- groups based on their CSF in an Aβ42/40 ratio. We then evaluated four single molecule array (Simoa) Quanterix assays, quantifying single plasma analytes and ratios (p-tau217, p-tau217/Aβ42 ratio, p-tau181, p-tau181/Aβ42 ratio and Aβ42/40 ratio) in their ability to distinguish between these groups and the effect of age.
The median (range) age of participants was 66 (55-79) years with 48 females (43.2%). The areas under the curve (AUC), not accounting for age, for the ability to discriminate Aβ+ from Aβ- groups were plasma p-tau217 AUC=0.94, Aβ42/40 AUC=0.78 and p-tau181 AUC=0.77. Combining p-tau217/Aβ42 increased the AUC to 0.97. The difference between the groups was influenced by age with less separation in older individuals: a significant negative interaction term between age and group for plasma p-tau217 concentrations (-0.037, p=0.013) and p-tau217/Aβ42 ratio (-0.007, p=0.008).
There was variable performance of plasma biomarkers to recapitulate the CSF assay. Both p-tau217 and p-tau217/Aβ42 showed excellent promise as surrogates of CSF amyloid status, although with slightly reduced performance in older individuals. There was poorer discriminatory ability for p-tau181 and Aβ42/40. Further research is needed to address potential age-related confounds.
在国民保健服务（NHS）认知障碍诊所所观察到的年龄范围内，血浆生物标志物以及脑脊液（CSF）能否用于区分淀粉样β蛋白阳性（Aβ+）和淀粉样β蛋白阴性（Aβ-）组？
作为对111例同时采集了血液和脑脊液样本的门诊患者进行常规诊断调查的一部分，根据脑脊液中Aβ42/40的比例将患者分为Aβ+组和Aβ-组。然后我们评估了四种单分子阵列（Simoa）Quanterix检测方法，对单个血浆分析物和比率（p-tau217、p-tau217/Aβ42比率、p-tau181、p-tau181/Aβ42比率以及Aβ42/40比率）区分这些组的能力以及年龄的影响进行了量化。
参与者的年龄中位数（范围）为66（55 - 79）岁，女性48名（43.2%）。在不考虑年龄的情况下，血浆p-tau217区分Aβ+组和Aβ-组的曲线下面积（AUC）为0.94，Aβ42/40的AUC为0.78，p-tau181的AUC为0.77。将p-tau217/Aβ42相结合可使AUC提高至0.97。组间差异受年龄影响，老年个体的区分度较低：血浆p-tau217浓度（-0.037，p = 0.013）以及p-tau217/Aβ42比率（-0.007，p = 0.008）在年龄和组之间存在显著的负交互项。
血浆生物标志物在重现脑脊液检测结果方面表现各异。p-tau217和p-tau217/Aβ42作为脑脊液淀粉样蛋白状态的替代指标均显示出良好前景，尽管在老年个体中性能略有下降。p-tau181和Aβ42/40的鉴别能力较差。需要进一步研究以解决潜在的年龄相关混杂因素。
