Bouras Constantin, Riederer Beat M, Kövari Enikö, Hof Patrick R, Giannakopoulos Panteleimon
Department of Psychiatry, University Hospitals of Geneva, 1225 Geneva, Switzerland.
Brain Res Brain Res Rev. 2005 Jun;48(3):477-87. doi: 10.1016/j.brainresrev.2004.09.009. Epub 2004 Oct 28.
Although the contribution of inflammatory processes in the etiology of late-onset Alzheimer's disease (AD) has been suspected for years, most studies were confined to the analysis of cell-mediated immunological reactions thought to represent an epiphenomenon of AD lesion development. Based on the traditional view of the "immunological privilege" of the brain, which excludes a direct access of human immunoglobulins (Ig) to the central nervous system under normal conditions, little attention has been paid to a possible role of humoral immunity in AD pathogenesis. In the first part of this review, we summarize evidences for a blood-brain barrier (BBB) dysfunction in this disorder and critically comment on earlier observations supporting the presence of anti-brain autoantibodies and immunoglobulins (Ig) in AD brains. Current concepts regarding the Ig turnover in the central nervous system and the mechanisms of glial and neuronal Fc receptors activation are also discussed. In the second part, we present new ex vivo and in vitro data suggesting that human immunoglobulins can interact with tau protein and alter both the dynamics and structural organization of microtubules. Subsequent experiments needed to test this new working hypothesis are addressed at the end of the review.
尽管炎症过程在晚发性阿尔茨海默病（AD）病因学中的作用多年来一直受到怀疑，但大多数研究局限于对细胞介导的免疫反应的分析，这些反应被认为是AD病变发展的一种附带现象。基于大脑“免疫特权”的传统观点，即在正常情况下人类免疫球蛋白（Ig）无法直接进入中枢神经系统，体液免疫在AD发病机制中的可能作用很少受到关注。在本综述的第一部分，我们总结了该疾病中血脑屏障（BBB）功能障碍的证据，并对早期支持AD大脑中存在抗脑自身抗体和免疫球蛋白（Ig）的观察结果进行了批判性评论。还讨论了关于中枢神经系统中Ig周转以及胶质细胞和神经元Fc受体激活机制的当前概念。在第二部分，我们展示了新的体外和体内数据，表明人类免疫球蛋白可以与tau蛋白相互作用，并改变微管的动力学和结构组织。综述结尾讨论了检验这一新工作假设所需的后续实验。
