Measuremrnt of laminins in cerebrospinal fluid (CSF) obtained from dementia using antibodies against laminin and laminin peptide -Developping a diagnostic biological marker-

本实验建立了一套针对层粘连蛋白-1、α5链、β1链、γ1链和层粘连蛋白肽（YFQRYLI）全链抗体的ELISA系统。利用该ELISA系统，我们测量了阿尔茨海默型痴呆（ATD）、血管性痴呆（VaD）和其他痴呆患者脑脊液中层粘连蛋白的水平，并与正常对照进行了比较。ATD组γ - 1链水平显著降低，且早发型AD的γ - 1水平随年龄增长而显著降低。另一方面，晚发性AD组的层粘连蛋白肽（YFQRYLI）水平明显高于早发性AD组和正常对照组。VaD组全层粘连蛋白-1和β1链水平显著升高。这些结果提示，层粘连蛋白或其衍生物可能与ATD和VaD的发病机制有关，防止层粘连蛋白水解可能是预防或减缓ATD进展的有效治疗方法。此外，利用脑脊液tau蛋白与脑脊液全层粘连蛋白-1的比值测定脑脊液层粘连蛋白诊断ATD的方法显示了有效的诊断敏感性（81%）和特异性（85%）。这些结果表明，脑脊液层粘连蛋白的测定可能是有用的诊断AD和VaD的生物学标志物。

We developed a new ELISA system using antibodies against whole laminin-1, α5 chain, β1 chain, γ1 chain and laminin peptide (YFQRYLI). Using this ELISA system, we measured laminin levels in CSF obtained from Alzheimer type dementia (ATD), vascular dementia (VaD) and other dementia comparing with normal controls. ATD group showed a significantly lower level of γ1 chain, and the γ1 level of early -onset AD was significantly decreased with aging. On the other hand, late onset AD group showed a significantly higher level of laminin peptide (YFQRYLI) than early-onset AD group and normal controls. VaD group showed a significantly higer level of whole laminin-1 and β1 chain. These results suggest that laminin or its derivatives may correlate to pathogenesis of ATD and VaD, and that the preventing of laminin proteolysis may be an effective therapeutic method for preventing or slowing down the progression of ATD.Furthermore, the assay of CSF laminin for the diagnosis of ATD showed efficient diagnostic sensitivity (81%) and specificity (85%) by using the ratio of CSF tau to CSF whole laminin-1. These findings suggest that the assay of CSF laminin may be useful as a diagnostic biological marker of AD and VaD.