Center for Translational Research in Biomedical Sciences, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Neurobiol Dis. 2011 Sep;43(3):698-705. doi: 10.1016/j.nbd.2011.05.023. Epub 2011 Jun 6.
Increasing evidence has shown that the immunological reaction of leukocytes plays a crucial role in the development of neurodegenerative disorders. We conducted transcriptome analysis of leukocytes from patients of mild cognitive impairment (MCI), Alzheimer's disease (AD), as well as normal controls (NC) by oligonucleotide microarray. The differentially expressed genes of interest were selected by pathway-based functional enrichment and were then validated in 60 subjects (17 NC, 20 MCI and 23 AD) by quantitative PCR (QRT-PCR). Thirty-four differentially expressed genes between NC and AD were enriched in ATP-binding cassette (ABC) transporters, ascorbate and aldarate metabolism, Gly/Ser/Thr metabolism, transforming growth factor-β signaling, and extracellular matrix (ECM)-receptor interaction pathways (Welch t-test; p < 0.05). Comparison of NC, MCI and AD transcriptomes identified 8 genes significantly associated with purine metabolism and the ABC transporters. Furthermore, 13 out of 18 genes selected from the above lists were successfully validated by QRT-PCR (Mann-Whitney U-test), and only ABCB1 gene exhibited significantly positive correlation with MMSE scores among NC, MCI, and AD subjects (r = 0.3858, p = 0.0011). With a limited number of study population, our study may provide a novel direction for evaluating diagnostic biomarkers in monitoring AD progression.
越来越多的证据表明，白细胞的免疫反应在神经退行性疾病的发展中起着至关重要的作用。我们通过寡核苷酸微阵列对轻度认知障碍（MCI）、阿尔茨海默病（AD）患者和正常对照（NC）的白细胞进行了转录组分析。通过基于途径的功能富集选择了感兴趣的差异表达基因，并通过定量 PCR（QRT-PCR）在 60 名受试者（17 名 NC、20 名 MCI 和 23 名 AD）中进行了验证。NC 和 AD 之间的 34 个差异表达基因富集在 ATP 结合盒（ABC）转运蛋白、抗坏血酸和醛酸代谢、甘氨酸/丝氨酸/苏氨酸代谢、转化生长因子-β信号和细胞外基质（ECM）-受体相互作用途径中（Welch t 检验；p < 0.05）。NC、MCI 和 AD 转录组的比较确定了 8 个与嘌呤代谢和 ABC 转运蛋白显著相关的基因。此外，从上述列表中选择的 18 个基因中的 13 个通过 QRT-PCR 成功验证（Mann-Whitney U 检验），并且仅 ABCB1 基因在 NC、MCI 和 AD 受试者中与 MMSE 评分呈显著正相关（r = 0.3858，p = 0.0011）。由于研究人群数量有限，我们的研究可能为评估 AD 进展监测中的诊断生物标志物提供了新的方向。
