Finch Caleb E, Morgan Todd E
Davis School of Gerontology and USC College, Dept. Biological Sciences, University of Southern California, Los Angeles, CA 90089-0191, USA.
Curr Alzheimer Res. 2007 Apr;4(2):185-9. doi: 10.2174/156720507780362254.
Alzheimer disease (AD) includes inflammatory processes in the senile plaques and surrounding glia, with increased expression of acute phase proteins such as C-reactive protein (CRP) and IL-6. Increased IL-6 expression during normal brain aging suggests a link of age-related inflammation to the onset of AD during aging. Blood levels of CRP and IL-6 are also associated with higher risk of Alzheimer disease and cognitive decline during aging. Some infections are known to induce inflammation and amyloid deposits. For example, HIV induces the deposition of the same beta-amyloid as in Alzheimer disease. The ApoE4 allele may increase HIV-associated dementia, in addition to its well-known effect on accelerating the onset age of AD. Many other adverse effects of apoE4 are recognized, which suggested the hypothesis that apoE4 persists in human populations because of balancing selection (Charlesworth-Martin hypothesis). The apoE4 allele was acquired during human evolution and may have conferred initial advantages in pathogen resistance. As evidence for this hypothesis, apoE4 carriers have less severe liver damage during hepatitis C infections. As human lifespan lengthened and cognitive and cardiovascular health became more important, the apoE3 allele spread, while the E4 allele was maintained in all populations by balancing selection.
阿尔茨海默病（AD）包括老年斑及周围神经胶质中的炎症过程，急性期蛋白如C反应蛋白（CRP）和白细胞介素-6（IL-6）的表达增加。正常脑老化过程中IL-6表达增加表明与年龄相关的炎症与老化过程中AD的发病存在关联。血液中CRP和IL-6水平也与阿尔茨海默病风险增加及老化过程中的认知衰退相关。已知一些感染会诱发炎症和淀粉样蛋白沉积。例如，HIV会诱导与阿尔茨海默病中相同的β-淀粉样蛋白沉积。除了其对加速AD发病年龄的众所周知的作用外，载脂蛋白E4（ApoE4）等位基因可能会增加与HIV相关的痴呆。ApoE4的许多其他不良反应也已得到认可，这提示了一个假说，即由于平衡选择（查尔斯沃思 - 马丁假说），ApoE4在人群中持续存在。ApoE4等位基因是在人类进化过程中获得的，可能在病原体抗性方面赋予了最初的优势。作为这一假说的证据，ApoE4携带者在丙型肝炎感染期间肝脏损伤较轻。随着人类寿命延长以及认知和心血管健康变得更加重要，ApoE3等位基因得以传播，而E4等位基因则通过平衡选择在所有人群中得以保留。
