Down syndrome individuals with Alzheimer's disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer's disease.
Down syndrome individuals with Alzheimer's disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer's disease.
复制标题
与散发性阿尔茨海默病相比，患有阿尔茨海默病的唐氏综合症患者具有独特的神经炎症表型。
DOI：
10.1016/j.neurobiolaging.2015.05.016
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发表时间：
2015
影响因子：
4.2
通讯作者：
Head,Elizabeth
中科院分区：
文献类型：
--
作者：
Wilcock,DonnaM;Hurban,Jennifer;Helman,AlexM;Sudduth,TiffanyL;McCarty,KatieL;Beckett,TinaL;Ferrell,JoshuaC;Murphy,MPaul;Abner,ErinL;Schmitt,FrederickA;Head,Elizabeth
唐氏综合症(DS)是导致智力残疾的最常见的遗传原因，主要由21号染色体的三倍体引起。淀粉样前体蛋白基因的过度表达可能足以推动阿尔茨海默病(AD)的神经病理，这种病理在几乎所有40岁前的DS患者中都能观察到。关于DS大脑中的炎症以及DS的遗传学如何改变这种疾病的炎症反应和改变AD的发病过程的信息相对较少。使用巨噬细胞M1、M2a、M2b和M2c炎症表型的分类系统，我们已经表明AD的早期阶段与偏向M1或M2a表型有关。在AD的晚期，M1、M2a和M2c的标志物升高。我们现在报告DS尸检系列中的炎症表型，以与散发性AD的进展进行比较。年轻DS患者(40岁以下，AD前)的组织显示偏向M1和M2b状态，很少观察到M2a或M2c。年龄较大的DS患者(40岁以上伴AD病理)表现出明显的偏向M2B表型。重要的是，这不同于散发性AD，后者的M2B表型很少，如果在尸检研究中观察到的话。在小胶质细胞免疫复合物激活和Toll样受体激活的刺激下，M2B表型代表了疾病脑中一种独特的神经炎症状态，可能对DS患者的治疗干预具有重要意义。
Down syndrome (DS) is the most common genetic cause of intellectual disability and is primarily caused by the triplication of chromosome 21. The overexpression of amyloid precursor protein gene may be sufficient to drive Alzheimer's disease (AD) neuropathology that is observed in virtually all individuals with DS by the age of 40 years. There is relatively little information about inflammation in the DS brain and how the genetics of DS may alter inflammatory responses and modify the course of AD pathogenesis in this disorder. Using the macrophage classification system of M1, M2a, M2b, and M2c inflammatory phenotypes, we have shown that the early stages of AD are associated with a bias toward an M1 or M2a phenotype. In later stages of AD, markers of M1, M2a and M2c are elevated. We now report the inflammatory phenotype in a DS autopsy series to compare this with the progression in sporadic AD. Tissue from young DS cases (under 40 years of age, pre-AD) show a bias toward M1 and M2b states with little M2a or M2c observed. Older DS cases (over 40 with AD pathology) show a distinct bias toward an M2b phenotype. Importantly, this is distinct from sporadic AD where the M2b phenotype has been rarely, if ever observed in postmortem studies. Stimulated by immune complex activation of microglial cells and toll-like receptor activation, the M2b phenotype represents a unique neuroinflammatory state in diseased brain and may have significant implications for therapeutic intervention for persons with DS.