Harpin M L, Delaère P, Javoy-Agid F, Bock E, Jacque C, Delpech B, Villarroya H, Duyckaerts C, Hauw J J, Baumann N
INSERM Neurobiology Unit 134, Neuropathology Laboratory Raymond Escourolle, France, Paris.
J Neurosci Res. 1990 Dec;27(4):587-94. doi: 10.1002/jnr.490270420.
The aim of this study was to compare brain glial fibrillary acidic protein (GFAP) levels to the modifications of cognitive functions (Blessed test score [BTS]), the density of the main neuropathological lesions (senile plaques [SP] and neurofibrillary tangles [NFT]), and the density of the two main subtypes of beta A4 deposits (classic plaques and diffuse deposits) in a series of patients with normal aging and senile dementia of the Alzheimer type of various degrees of severity. GFAP levels (enzyme-linked immunosorbent assay [ELISA] technique) and the densities of changes were measured in the temporal lobe of 12 women over 75 years of age. Under these conditions, the ELISA assay could determine GFAP in brain homogenates (aqueous-Triton buffer soluble extract) in a range from 2.5 ng to 600 ng per assay. Least affected patients (with a BTS of 19 and over) all ranged below 60 micrograms/mg protein. Most affected patients (with a BTS under 6) ranged above 150 micrograms/mg protein. However, interindividual variations were wide. A significant correlation between the BTS and the amount of GFAP could be found only when using the non parametric test of Spearman. There was a significant positive correlation between the amount of GFAP and the density of 1) SP, 2) NFT both revealed by Bodian's silver stain, and 3) classic beta A4 plaques shown by immunocytochemistry. On the contrary, no correlation was observed with diffuse beta A4 deposits. One case with very large amounts of diffuse beta A4 deposits without SP or NFT showed no associated GFAP reactivity. This suggests that GFAP production is a critical event in the formation of classic SP.
本研究的目的是比较一系列不同严重程度的正常衰老和阿尔茨海默型老年痴呆患者的脑胶质纤维酸性蛋白(GFAP)水平与认知功能改变(布雷斯德测试评分[BTS])、主要神经病理病变(老年斑[SP]和神经原纤维缠结[NFT])的密度以及β淀粉样蛋白(Aβ)沉积的两种主要亚型(经典斑块和弥漫性沉积)的密度。采用酶联免疫吸附测定(ELISA)技术测量了12名75岁以上女性颞叶中的GFAP水平及变化密度。在这些条件下,ELISA测定法能够测定脑匀浆(水 - 曲拉通缓冲液可溶性提取物)中每次测定范围为2.5 ng至600 ng的GFAP。受影响最小的患者(BTS为19及以上)均低于60微克/毫克蛋白质。受影响最大的患者(BTS低于6)则高于150微克/毫克蛋白质。然而,个体间差异很大。仅使用Spearman非参数检验时,才能发现BTS与GFAP量之间存在显著相关性。GFAP量与以下各项的密度之间存在显著正相关:1)经博迪安银染显示的SP,2)NFT,以及3)经免疫细胞化学显示的经典β淀粉样蛋白斑块。相反,未观察到与弥漫性β淀粉样蛋白沉积有相关性。有一例患者有大量弥漫性β淀粉样蛋白沉积,但无SP或NFT,未显示相关的GFAP反应性。这表明GFAP的产生是经典SP形成中的关键事件。