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.

我们开发了一种新的 ELISA 系统，使用针对整个层粘连蛋白-1、α5 链、β1 链、γ1 链和层粘连蛋白肽 (YFQRYLI) 的抗体。使用该 ELISA 系统，我们测量了从阿尔茨海默型痴呆 (ATD)、血管性痴呆 (VaD) 和其他痴呆症中获得的脑脊液中层粘连蛋白的水平，并与正常对照进行比较。 ATD组γ1链水平显着降低，且早发性AD的γ1水平随年龄增长显着降低。另一方面，晚发AD组的层粘连蛋白肽（YFQRYLI）水平显着高于早发AD组和正常对照。 VaD 组的整个层粘连蛋白-1 和β1 链的水平显着较高。这些结果表明，层粘连蛋白或其衍生物可能与 ATD 和 VaD 的发病机制相关，并且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，通过使用 CSF 层粘连蛋白的比值，用于诊断 ATD 的 CSF 层粘连蛋白检测显示出有效的诊断灵敏度（81%）和特异性（85%）。 CSF tau 到 CSF 全层粘连蛋白-1。这些发现表明，CSF 层粘连蛋白的测定可用作 AD 和 VaD 的诊断生物标志物。