Kálmán J, Kitajka K, Pákáski M, Zvara A, Juhász A, Vincze G, Janka Z, Puskás L G
Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Semmelweis u. 6. H-6725 Szeged, Hungary.
Psychiatr Genet. 2005 Mar;15(1):1-6. doi: 10.1097/00041444-200503000-00001.
Since the function and metabolism of peripheral lymphocytes is known to be altered in Alzheimer's disease (AD), a pilot study was carried out to examine differences in gene expression profiles of these cells in 16 AD patients and aged control probands. Using a cDNA microarray representing 3200 distinct human genes, we identified 20 candidate genes whose expression is altered in AD lymphocytes compared with the control probands. Among these were the alpha2C-adrenoreceptor gene, known to regulate blood pressure and learning, the defensin, histocompability complex enhancer-binding protein, carboxypeptidase M, and the Fc fragment of IgE known to be involved in cellular and humoral immune responses. Others, like human cell death protein, TRAIL, and galectin-4 participate in the regulation of apoptosis. Real-time quantitative reverse transcription-polymerase chain reaction analysis was performed in order to confirm the expression changes in AD lymphocytes, and it could detect down-regulation of defensin and alpha2c-adrenoceptor genes, while other genes seemed unaltered in their expression, including heat-shock protein (hsp90), cholesteryl ester transfer protein, and apolipoprotein B100 (apoB). The altered expression profile of these genes might be connected with the previously reported AD-specific lymphocyte abnormalities. It remains to be elucidated, however, how these genes are related to the pathomechanism of dementia and whether the gene expression differences of AD lymphocytes reflect disease traits or stage processes.
由于已知阿尔茨海默病（AD）患者外周淋巴细胞的功能和代谢会发生改变，因此开展了一项初步研究，以检测16例AD患者和老年对照者这些细胞的基因表达谱差异。我们使用代表3200个不同人类基因的cDNA微阵列，鉴定出20个候选基因，其在AD淋巴细胞中的表达与对照者相比发生了改变。其中包括已知可调节血压和学习能力的α2C肾上腺素能受体基因、防御素、组织相容性复合体增强子结合蛋白、羧肽酶M以及已知参与细胞免疫和体液免疫反应的IgE的Fc片段。其他基因，如人类细胞死亡蛋白、肿瘤坏死因子相关凋亡诱导配体（TRAIL）和半乳糖凝集素-4，则参与细胞凋亡的调节。为了确认AD淋巴细胞中的表达变化，我们进行了实时定量逆转录-聚合酶链反应分析，结果发现防御素和α2c-肾上腺素能受体基因表达下调，而其他基因的表达似乎未发生改变，包括热休克蛋白（hsp90）、胆固醇酯转运蛋白和载脂蛋白B100（apoB）。这些基因表达谱的改变可能与先前报道的AD特异性淋巴细胞异常有关。然而，这些基因如何与痴呆的发病机制相关，以及AD淋巴细胞的基因表达差异是否反映疾病特征或病程，仍有待阐明。
