High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis

Objective: We examined whether plasma Aβ42/Aβ40, as measured by a high precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF pTau181/Aβ42 as reference standards.
Methods: Using an immunoprecipitation and liquid chromatography-mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within eighteen months of an amyloid PET scan.
Results: Plasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (ROC AUC 0.88, 95% confidence intervals [CI] 0.82-0.93) and CSF pTau181/Aβ42 (AUC 0.85, 95% CI 0.79-0.92). The combination of plasma Aβ42/Aβ40, age and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90-0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Aβ42/Aβ40 (p=0.01).
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研究目的：本研究旨在探讨经高精度检测方法测定的血浆Aβ42/Aβ40比值，以淀粉样蛋白PET（amyloid PET）或脑脊液（CSF）磷酸化tau蛋白181位点/Aβ42作为参考标准，能否准确诊断脑淀粉样变性。
研究方法：本研究采用免疫沉淀联合液相色谱-质谱联用（immunoprecipitation and liquid chromatography-mass spectrometry）检测方法，对158名多数认知功能正常的受试者的血浆与脑脊液样本中的Aβ42/Aβ40比值进行测定，所有样本均采集于淀粉样蛋白PET扫描前18个月内。
研究结果：血浆Aβ42/Aβ40比值与淀粉样蛋白PET检测结果具有较高的一致性（受试者工作特征曲线下面积（ROC AUC）=0.88，95%置信区间（95% CI）为0.82~0.93），与脑脊液pTau181/Aβ42比值的一致性亦较高（AUC=0.85，95% CI 0.79~0.92）。将血浆Aβ42/Aβ40比值、年龄及载脂蛋白Eε4（APOE ε4）状态相结合后，与淀粉样蛋白PET检测结果的一致性显著提升（AUC=0.94，95% CI 0.90~0.97）。基线淀粉样蛋白PET检测呈阴性，但血浆Aβ42/Aβ40比值阳性（阈值<0.1218）的受试者，其转化为淀粉样蛋白PET阳性的风险是血浆Aβ42/Aβ40比值阴性受试者的15倍（p=0.01）。（原文后续内容截断）