Verbeek M M, Otte-Höller I, Westphal J R, Wesseling P, Ruiter D J, de Waal R M
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Am J Pathol. 1994 Jan;144(1):104-16.
The still unsolved pathogenesis of Alzheimer's disease (AD) has been the subject of extensive speculation. Some years ago, a local acute phase reaction involving production of interleukin-1 (IL-1) and IL-6 was proposed as the triggering event in AD. Since it has been reported that these cytokines induce expression of intercellular adhesion molecule-1 (ICAM-1), we analyzed AD brain tissue cryosections for the presence of ICAM-1 by immunostaining and for ICAM-2 expression as a control. In senile plaques a marked diffuse or granular staining for the ICAM-1 domains 1, 4, and 5 was observed, whereas ICAM-2 expression was observed in microglial cells. Immunoprecipitation analysis demonstrated the presence of a 85 kd ICAM-1 molecule in AD frontal cortex. Our findings indicate that ICAM-1 accumulates in senile plaques as a complete 5-domain molecule at a relatively early stage of senile plaque formation. Our results are in support of a cytokine-mediated pathogenesis of senile plaque formation.
阿尔茨海默病(AD)尚未解决的发病机制一直是广泛推测的主题。几年前,有人提出涉及白细胞介素-1(IL-1)和IL-6产生的局部急性期反应是AD的触发事件。由于有报道称这些细胞因子可诱导细胞间粘附分子-1(ICAM-1)的表达,我们通过免疫染色分析了AD脑组织冰冻切片中ICAM-1的存在情况,并以ICAM-2的表达作为对照。在老年斑中观察到ICAM-1结构域1、4和5有明显的弥漫性或颗粒状染色,而在小胶质细胞中观察到ICAM-2的表达。免疫沉淀分析表明AD额叶皮质中存在一个85 kd的ICAM-1分子。我们的研究结果表明,ICAM-1在老年斑形成的相对早期以完整的5结构域分子形式在老年斑中积累。我们的结果支持细胞因子介导的老年斑形成发病机制。