Giannakopoulos P, Bouras C, Kövari E, Shioi J, Tezapsidis N, Hof P R, Robakis N K
Department of Psychiatry, University of Geneva School of Medicine, Switzerland.
Am J Pathol. 1997 Feb;150(2):429-36.
Recent studies have suggested that missense mutations in the presenilin-1 gene are causally related to the majority of familial early-onset Alzheimer's disease (AD). To examine the possible involvement of presenilin-1 in late-onset sporadic AD, a quantitative analysis of its distribution in the cerebral cortex of nondemented and AD patients was performed using immunocytochemistry. Stereological analyses revealed that AD brains showed a marked neuronal loss in the CA1 field of the hippocampus and hilus of the dentate gyrus, subiculum, and entorhinal cortex. In these areas, however, the fraction of neurofibrillary tangle (NFT)-free neurons showing presenilin-1 immunoreactivity was increased compared with nondemented controls. In contrast, cortical areas, which displayed no neuronal loss, did not show any significant increase in the fraction of presenilin-1-positive neurons. Moreover, presenilin-1 immunoreactivity was reduced in NFT-containing neurons. Thus, in AD, the fraction of NFT-free neurons that contained presenilin-1 varied from 0.48 to 0.77, whereas the fraction of NFT-containing neurons that were presenilin-1 positive varied from 0.1 to 0.24. Together, these observations indicate that presenilin-1 may have a neuroprotective role and that in AD low cellular expression of this protein may be associated with increased neuronal loss and NFT formation.
最近的研究表明，早老素-1基因中的错义突变与大多数家族性早发型阿尔茨海默病（AD）存在因果关系。为了研究早老素-1在晚发型散发性AD中可能的作用，我们采用免疫细胞化学方法对非痴呆患者和AD患者大脑皮质中早老素-1的分布进行了定量分析。体视学分析显示，AD患者大脑海马CA1区、齿状回门、下托和内嗅皮质存在明显的神经元丢失。然而，在这些区域，与非痴呆对照组相比，未出现神经原纤维缠结（NFT）的神经元中早老素-1免疫反应性增加。相比之下，未出现神经元丢失的皮质区域，早老素-1阳性神经元的比例没有显著增加。此外，含NFT的神经元中早老素-1免疫反应性降低。因此，在AD中，不含NFT的神经元中早老素-1的比例在0.48至0.77之间，而含NFT的神经元中早老素-1阳性的比例在0.1至0.24之间。这些观察结果共同表明，早老素-1可能具有神经保护作用，并且在AD中该蛋白的低细胞表达可能与神经元丢失增加和NFT形成有关。
