Tobinick Edward L, Gross Hyman
Department of Medicine, Institute for Neurological Research, Los Angeles, USA.
J Neuroinflammation. 2008 Jan 9;5:2. doi: 10.1186/1742-2094-5-2.
Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligomers. The efficacy of etanercept, a biologic antagonist of TNF-alpha, delivered by perispinal administration, for treatment of Alzheimer's disease over a period of six months has been previously reported in a pilot study. This report details rapid cognitive improvement, beginning within minutes, using this same anti-TNF treatment modality, in a patient with late-onset Alzheimer's disease. Rapid cognitive improvement following perispinal etanercept may be related to amelioration of the effects of excess TNF-alpha on synaptic mechanisms in Alzheimer's disease and provides a promising area for additional investigation and therapeutic intervention.
大量基础科学和临床证据表明，过量的肿瘤坏死因子-α（TNF-α）在阿尔茨海默病的发病机制中起核心作用。除了其促炎功能外，TNF-α最近还被认为是一种神经胶质递质，可调节神经网络中的突触功能。TNF-α最近还被证明可介导由β-淀粉样蛋白和β-淀粉样蛋白寡聚体引起的突触记忆机制破坏。在一项初步研究中，先前已报道了通过脊柱旁给药的TNF-α生物拮抗剂依那西普治疗阿尔茨海默病六个月的疗效。本报告详细介绍了一名晚发性阿尔茨海默病患者使用相同的抗TNF治疗方式后，在数分钟内开始出现快速认知改善的情况。脊柱旁注射依那西普后快速的认知改善可能与改善过量TNF-α对阿尔茨海默病突触机制的影响有关，并为进一步研究和治疗干预提供了一个有前景的领域。
