The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA.
Biomarkers. 2009 Nov;14(7):493-501. doi: 10.3109/13547500903108423.
The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer's disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included Abeta1-40, Abeta1-42, total tau, phosphorylated tau, alpha-1 acid glycoprotein (A1GP), haptoglobin, zinc alpha-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of Abeta1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND and NADD subjects. Logistic regression analysis for the diagnostic discrimination of AD from ND found that Abeta1-42, ApoA1 and HPX each had significant and independent associations with diagnosis. The CSF concentrations of these three markers distinguished AD from ND subjects with 84% sensitivity and 72% specificity, with 78% of subjects correctly classified. By comparison, using Abeta1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects correctly classified. For the diagnostic discrimination of AD from NADD, only the concentration of Abeta1-42 was significantly related to diagnosis, with a sensitivity of 58%, specificity of 86% and 86% correctly classified. The results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including Abeta1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Abeta1-42 alone. For the discrimination of AD from NADD subjects, measurement of Abeta1-42 alone was superior.
我们评估了几种候选脑脊液（CSF）蛋白生物标志物在神经病理学确诊的阿尔茨海默病（AD）、非痴呆（ND）老年对照和非 AD 痴呆（NADD）患者中的诊断性能。候选标志物是基于初步的二维凝胶电泳研究或文献综述选择的。前者方法选择的标志物包括载脂蛋白 A-1（ApoA1）、血红素结合蛋白（HPX）、转甲状腺素蛋白（TTR）和色素上皮衍生因子（PEDF），而文献中确定的标志物包括 Abeta1-40、Abeta1-42、总 tau、磷酸化 tau、α-1 酸性糖蛋白（A1GP）、触珠蛋白、锌-α-2 糖蛋白（Z2GP）和载脂蛋白 E（ApoE）。通过酶联免疫吸附试验（ELISA）测量标志物的脑室 CSF 浓度。Abeta1-42、ApoA1、A1GP、ApoE、HPX 和 Z2GP 的浓度在 AD、ND 和 NADD 受试者之间差异显著。AD 与 ND 鉴别诊断的逻辑回归分析发现，Abeta1-42、ApoA1 和 HPX 与诊断均有显著的独立关联。这三个标志物的 CSF 浓度可将 AD 与 ND 受试者区分开来，敏感性为 84%，特异性为 72%，78%的受试者正确分类。相比之下，单独使用 Abeta1-42 的敏感性为 79%，特异性为 61%，68%的受试者正确分类。对于 AD 与 NADD 的鉴别诊断，只有 Abeta1-42 的浓度与诊断显著相关，敏感性为 58%，特异性为 86%，86%的受试者正确分类。结果表明，对于 AD 与 ND 对照组的鉴别诊断，与单独测量 Abeta1-42 相比，测量一组包括 Abeta1-42、ApoA1 和 HPX 的标志物可提高诊断性能。对于 AD 与 NADD 患者的鉴别诊断，单独测量 Abeta1-42 更具优势。
