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

我们建立了一种新的ELISA体系，该体系使用抗层粘连蛋白1（laminin-1）、α5链、β1链、γ1链和层粘连蛋白肽（laminin peptide，YLYLI）的抗体。应用该ELISA系统检测了阿尔茨海默型痴呆（ATD）、血管性痴呆（VaD）及其他痴呆患者脑脊液中层粘连蛋白的含量，并与正常对照组进行比较。ATD组表现为γ1链水平明显降低，早发AD的γ1水平随增龄而明显降低。另一方面，晚发性AD组的层粘连蛋白肽（YL-RYLI）水平显著高于早发性AD组和正常对照组。VaD组LN-1和β1链表达明显高于对照组。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延缓ATD进展的有效治疗方法。此外，CSF层粘连蛋白检测对ATD诊断的敏感性（81%）和特异性（85%）均较好。这些结果表明，CSF层粘连蛋白的测定可能是有用的AD和VaD的诊断生物学标记物。

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.