Salza Romain, Oudart Jean-Baptiste, Ramont Laurent, Maquart François-Xavier, Bakchine Serge, Thoannès Henri, Ricard-Blum Sylvie
Bases Moléculaires et Structurales des Systèmes Infectieux, UMR 5086 CNRS, Université Lyon 1, Institut de Biologie et Chimie des Protéines, Lyon, France.
CHU de Reims, Laboratoire Central de Biochimie, Reims, France Université de Reims Champagne-Ardenne, CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, Reims, France.
J Alzheimers Dis. 2015;44(4):1253-61. doi: 10.3233/JAD-142544.
The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-β1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-β1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD.
本研究的目的是测量神经退行性疾病患者脑脊液(CSF)中内皮抑素的水平,内皮抑素是胶原蛋白 XVIII 的一个片段,在阿尔茨海默病(AD)患者的大脑中会蓄积。通过酶联免疫吸附测定法测量了 AD 患者(n = 57)、行为性额颞叶痴呆(bvFTD,n = 22)、非 AD 和非 FTD 痴呆(nAD/nFTD,n = 84)以及 45 名无神经退行性疾病受试者脑脊液中的总蛋白、内皮抑素、淀粉样β1-42 肽、tau 蛋白和过度磷酸化 tau 蛋白的浓度。通过 Mann-Whitney 检验、Kruskal 和 Wallis 检验以及 ROC 分析评估结果的统计学意义。在对照受试者和神经退行性疾病患者中,脑脊液中内皮抑素的浓度均高于 AD 的三种标志物水平。与对照组相比,AD 患者(257%,p < 0.0001)和 nAD/nFTD 患者(140%,p < 0.0001)的内皮抑素/淀粉样β1-42 比值显著升高。与对照组相比,AD 患者的内皮抑素/tau 蛋白比值显著降低(-49%,p < 0.0001),但 bvFTD 患者升高(89%,p < 0.0001)。同样,与对照组相比,AD 患者的内皮抑素/过度磷酸化 tau 蛋白比值降低(-21%,p = 0.0002),但 bvFTD 患者升高(81%,p = 0.0026)。测量脑脊液中的内皮抑素并计算其与成熟的 AD 标志物的比值,可改善 bvFTD 患者的诊断,并有助于区分 AD 患者与 bvFTD 和 nAD/nFTD 患者。