McGeer Patrick L, McGeer Edith G
University of British Columbia, Kinsmen Laboratory of Neurological Research , 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 , Canada
Expert Opin Ther Targets. 2015 Apr;19(4):497-506. doi: 10.1517/14728222.2014.988707. Epub 2014 Nov 29.
Activated microglia are associated with the progression of Alzheimer's disease (AD), as well as many other neurodegenerative diseases of aging. Microglia are therefore key targets for therapeutic intervention.
β-amyloid (Aβ) deposits activate the complement system, which, in turn, stimulates microglia to release neurotoxic materials. Research has focused primarily on anti-inflammatory agents to temper this toxic effect. More recently there has been a focus on converting microglia from this M1 state to an M2 state in which the toxic effects are reduced and their phagocytic activity toward Aβ enhanced. Studies in transgenic mice have suggested a number of possible anti-inflammatory approaches but they may not always be a good model. An example is vaccination with antibodies to Aβ, which is effective in mouse models, but has repeatedly failed in clinical trials. Biomarker studies indicate that AD commences many years prior to clinical onset.
A hopeful approach to a disease-modifying treatment of AD is to administer agents that inhibit the inflammatory stimulation of microglia or successfully convert them to an M2 state. However, any such treatment must be started early in the disease.
活化的小胶质细胞与阿尔茨海默病（AD）以及许多其他衰老相关的神经退行性疾病的进展有关。因此，小胶质细胞是治疗干预的关键靶点。
β-淀粉样蛋白（Aβ）沉积物激活补体系统，进而刺激小胶质细胞释放神经毒性物质。研究主要集中在使用抗炎剂来减轻这种毒性作用。最近，人们将重点放在将小胶质细胞从M1状态转变为M2状态，在M2状态下，毒性作用降低，对Aβ的吞噬活性增强。对转基因小鼠的研究提出了一些可能的抗炎方法，但它们可能并不总是一个好的模型。例如，用Aβ抗体进行疫苗接种，在小鼠模型中有效，但在临床试验中多次失败。生物标志物研究表明，AD在临床发病前许多年就已开始。
一种有望用于AD疾病修饰治疗的方法是给予抑制小胶质细胞炎症刺激或成功将其转变为M2状态的药物。然而，任何此类治疗都必须在疾病早期开始。
