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

使用针对层粘连蛋白和层粘连蛋白肽的抗体测量从痴呆症中获得的脑脊液（CSF）中的层粘连蛋白 -开发诊断生物标志物 -

• 批准号: 11670953
• 负责人: MATSUDA Kazunori
• 金额: $ 0.77万
• 依托单位: Miyazaki Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670953/
• 关键词: Laminin; Laminin peptide; Alzheimer's disease; Vascular dementia; ELISA; Cerebrospinal fluid; Diagnostic marker; Therapeutic agent; Therapeutic agent; ラミニンγ; wholeラミニン; ラミニンペプチド; 髄液; アルツハイマー病(AD); 脳血管性痴呆(VaD); βアミロイド

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.

我们利用抗层粘连蛋白-1、α-5链、β-1链、γ-1链和层粘连蛋白多肽的抗体建立了一种新的ELISA系统。应用该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水平，并与正常对照组进行了比较。阿尔茨海默病组γ-1链水平显著降低，且早发性AD患者γ-1水平随增龄而降低。另一方面，晚发性AD组的层粘连蛋白多肽(YFQRYLI)水平显著高于早发性AD组和正常对照组。VAD组的全层粘连蛋白-1和β-1链的表达水平明显高于对照组。这些结果提示，层粘连蛋白及其衍生物可能与ATD和VAD的发病机制有关，阻止层粘连蛋白的降解可能是预防或减缓ATD进展的有效治疗方法。此外，以脑脊液tau/CSF全层粘连蛋白-1的比值诊断ATD的敏感性(81%)和特异性(85%)是有效的。提示脑脊液中层粘连蛋白的测定可作为诊断AD和VAD的生物学标志物。