Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University, Von-Siebold-Str. 5, 37075, Goettingen, Germany.
Current address: McLean Hospital, Department of Psychiatry, Harvard Medical School, Translational Neuroscience Laboratory, Belmont, MA, 02478, USA.
Alzheimers Res Ther. 2022 Sep 7;14(1):127. doi: 10.1186/s13195-022-01071-y.
Measurements of the amyloid-β (Aβ) 42/40 ratio in blood plasma may support the early diagnosis of Alzheimer's disease and aid in the selection of suitable participants in clinical trials. Here, we compared the diagnostic performance of fully automated prototype plasma Aβ42/40 assays with and without pre-analytical sample workup by immunoprecipitation.
A pre-selected clinical sample comprising 42 subjects with normal and 38 subjects with low cerebrospinal fluid (CSF) Aβ42/40 ratios was studied. The plasma Aβ42/40 ratios were determined with fully automated prototype Elecsys® immunoassays (Roche Diagnostics GmbH, Penzberg, Germany) by direct measurements in EDTA plasma or after pre-analytical Aβ immunoprecipitation. The diagnostic performance for the detection of abnormal CSF Aβ42/40 was analyzed by receiver operating characteristic (ROC) analysis. In an additional post hoc analysis, a biomarker-supported clinical diagnosis was used as a second endpoint.
Pre-analytical immunoprecipitation resulted in a significant increase in the area under the ROC curve (AUC) from 0.73 to 0.88 (p = 0.01547) for identifying subjects with abnormal CSF Aβ42/40. A similar improvement in the diagnostic performance by pre-analytical immunoprecipitation was also observed when a biomarker-supported clinical diagnosis was used as a second endpoint (AUC increase from 0.77 to 0.92, p = 0.01576).
Our preliminary observations indicate that pre-analytical Aβ immunoprecipitation can improve the diagnostic performance of plasma Aβ assays for detecting brain amyloid pathology. The findings may aid in the further development of blood-based immunoassays for Alzheimer's disease ultimately suitable for screening and routine use.
血液血浆中淀粉样蛋白-β（Aβ）42/40 比值的测量可能有助于阿尔茨海默病的早期诊断，并有助于在临床试验中选择合适的参与者。在这里，我们比较了全自动原型血浆 Aβ42/40 分析物与无预分析样品免疫沉淀的分析物在诊断性能方面的差异。
我们研究了一个预先选择的临床样本，该样本包含 42 名脑脊液（CSF）Aβ42/40 比值正常的受试者和 38 名 CSF Aβ42/40 比值低的受试者。通过直接测量 EDTA 血浆或预分析 Aβ 免疫沉淀后，使用全自动原型 Elecsys®免疫分析（罗氏诊断公司，德国彭贝格）来确定血浆 Aβ42/40 比值。通过接收者操作特征（ROC）分析来分析检测异常 CSF Aβ42/40 的诊断性能。在一个额外的事后分析中，将生物标志物支持的临床诊断用作第二个终点。
预分析免疫沉淀导致 ROC 曲线下面积（AUC）从识别异常 CSF Aβ42/40 受试者的 0.73 增加到 0.88（p = 0.01547）。当使用生物标志物支持的临床诊断作为第二个终点时，预分析免疫沉淀也观察到了类似的诊断性能改善（AUC 从 0.77 增加到 0.92，p = 0.01576）。
我们的初步观察表明，预分析 Aβ 免疫沉淀可以提高检测脑淀粉样蛋白病理的血浆 Aβ 分析物的诊断性能。这些发现可能有助于进一步开发适合筛查和常规使用的基于血液的阿尔茨海默病免疫分析物。
