Parachikova A, Agadjanyan M G, Cribbs D H, Blurton-Jones M, Perreau V, Rogers J, Beach T G, Cotman C W
Institute for Brain Aging & Dementia, University of California, 1113 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, USA.
Neurobiol Aging. 2007 Dec;28(12):1821-33. doi: 10.1016/j.neurobiolaging.2006.08.014. Epub 2006 Oct 18.
Alzheimer disease (AD) is the most prominent cause of dementia in the elderly. To determine changes in the AD brain that may mediate the transition into dementia, the gene expression of approximately 10,000 full-length genes was compared in mild/moderate dementia cases to non-demented controls that exhibited high AD pathology. Including this latter group distinguishes this work from previous studies in that it allows analysis of early cognitive loss. Compared to non-demented high-pathology controls, the hippocampus of AD cases with mild/moderate dementia had increased gene expression of the inflammatory molecule major histocompatibility complex (MHC) II, as assessed with microarray analysis. MHC II protein levels were also increased and inversely correlated with cognitive ability. Interestingly, the mild/moderate AD dementia cases also exhibited decreased number of T cells in the hippocampus and the cortex compared to controls. In conclusion, transition into AD dementia correlates with increased MHC II(+) microglia-mediated immunity and is paradoxically paralleled by a decrease in T cell number, suggesting immune dysfunction.
阿尔茨海默病（AD）是老年人痴呆症最主要的病因。为了确定AD大脑中可能介导向痴呆症转变的变化，研究人员比较了轻度/中度痴呆症病例与表现出高度AD病理特征的非痴呆对照中约10000个全长基因的基因表达情况。纳入后一组使这项研究有别于以往的研究，因为它能够分析早期认知能力丧失情况。与非痴呆的高病理对照相比，通过微阵列分析评估发现，轻度/中度痴呆的AD病例海马体中炎症分子主要组织相容性复合体（MHC）II的基因表达增加。MHC II蛋白水平也升高，且与认知能力呈负相关。有趣的是，与对照组相比，轻度/中度AD痴呆症病例海马体和皮质中的T细胞数量也减少。总之，向AD痴呆症的转变与MHC II(+)小胶质细胞介导的免疫增加相关，且矛盾的是同时伴有T细胞数量减少，提示存在免疫功能障碍。
