Targeting inflammatory mechanisms in Alzheimer's disease.

阿尔茨海默病S病占痴呆症病例的大多数，也是澳大利亚养老院要求的最常见原因。这不是一种仅限于老年的疾病，因为它也会影响20多岁和30多岁的人。目前还没有治愈阿尔茨海默病的方法，很大程度上是因为根本原因尚不清楚。阿尔茨海默病患者大脑中淀粉样β蛋白的沉积被认为是导致痴呆的神经细胞丢失的原因。然而，淀粉样β蛋白沉积可以在没有痴呆和有显著神经细胞丢失的情况下发生，这表明存在另一种神经毒性机制。炎症是阿尔茨海默病大脑的一贯特征。我们有初步证据表明，炎症是阿尔茨海默病神经毒性的原因。我们最近观察到，由于基因突变，患有家族性阿尔茨海默病的患者大脑中一种不明蛋白质周围出现了显著的炎症反应。这种炎症反应与这些病例中所见的显著的淀粉样β蛋白沉积无关，这表明存在一种新的有效的炎症刺激。此外，这些病例有更大的神经细胞丢失和较短的病程，这两个指标都表明神经毒性增加。本研究旨在利用蛋白质和基因分析工具，确定炎症的毒性和推动阿尔茨海默病大脑这种反应的刺激，以及确定炎症介导的毒性对培养的神经细胞的程度。只有解决这些目标，我们才能集中精力开发安全有效的治疗策略来预防或治疗疾病过程。

Alzheimer s disease accounts for the majority of dementia cases and is the most common cause for nursing home requirements in Australia. It is not a disease that is confined to old age as it can also affect individuals in their 20s and 30s. There is currently no cure for Alzheimer's disease, largely because the underlying cause is unknown. Deposition of the amyloid-beta protein within the brain of Alzheimer's disease patients is thought to be responsible for the neuronal cell loss which underlies the dementia. However, amyloid-beta protein deposition can occur in the absence of dementia and in the asbence of significant neuronal cell loss, suggesting that an alternative mechanism of neurotoxicity exists. Inflammation is a consistent feature of the Alzheimer's disease brain. We have preliminary evidence to suggest that inflammation is responsible for the neurotoxicity in Alzheimer's disease. We have recently observed a significant inflammatory response surrounding an unidentified protein in the brains of individuals with a familial form of Alzheimer's disease due to a genetic mutation. This inflammatory response is not associated with the significant amyloid-beta protein deposition seen in these cases suggesting that a novel potent inflammatory stimulus exists. Furthermore, these cases have greater neuronal cell loss and a shorter disease duration, both indicators of increased neurotoxicity. The present study is designed to determine the toxicity of inflammation and the stimulus driving this response in the Alzheimer's disease brain using tools for protein and gene analysis, as well as determining the extent of inflammation-mediated toxicity on neuronal cells grown in culture. Only by addressing these aims can we concentrate on developing safe and effective therapeutic strategies to prevent or treat the disease process.