Mondal Tanmoy, Noreen Zarish, Loffredo Christopher A, Johnson Jheannelle, Bhatti Attya, Nunlee-Bland Gail, Quartey Ruth, Howell Charles D, Moses Gemeyel, Nnanabu Thomas, Cotin Sharleine T, Clark Marika, Chandra Vijay, Jana Siddhartha S, Kwabi-Addo Bernard, Korba Brent E, Shahzad Sharoon, Bhatti Muhammad Farrukh, Ghosh Somiranjan
Department of Biology, Howard University, Washington, DC, USA.
Department of Healthcare Biotechnology, National University of Sciences and Technology (NUST), Islamabad, Pakistan.
J Alzheimers Dis Rep. 2024 Mar 19;8(1):479-493. doi: 10.3233/ADR-230146. eCollection 2024.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan.
Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population.
To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; = 33 subjects) coupled with Affymetrix Arrays ( = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways.
We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in and . The global gene expression study observed that 61% and 39% of genes were significantly (-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., , , and . The top-scoring networks in Diseases and Disorders Development were , , and .
Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to , which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.
阿尔茨海默病（AD）是一种多因素神经退行性疾病，在老年人中最为常见，尤其是在发达国家，而在巴基斯坦等发展中国家其患病率目前也在上升。
在巴基斯坦人群的一项初步病例对照研究中，我们的目标是鉴定与AD发病机制相关的关键基因及其表达水平以及相关分子转录组网络。
为了获得与巴基斯坦AD患者发病机制相关的分子网络谱（比较病例组和对照组），我们使用高通量qRT-PCR（TaqMan低密度阵列；=33名受试者）结合Affymetrix阵列（=8）和 Ingenuity通路分析（IPA）来鉴定与淀粉样蛋白加工和疾病通路相关的特征基因。
我们确认了16个差异表达的AD相关基因，包括在[具体基因1]和[具体基因2]中观察到的最大倍数变化。整体基因表达研究观察到，与健康对照相比，AD患者中分别有61%和39%的基因显著上调（-值0.05）和下调。关键通路包括，例如[通路1]、[通路2]和[通路3]。疾病与病症发展中得分最高的网络是[网络1]、[网络2]和[网络3]。
我们的初步研究提供了一种非侵入性且高效的方法，通过在AD患者中利用全血结合TLDA和整体基因表达方法来研究基因表达模式。这为与[具体相关内容]相关基因的表达状态提供了有价值的见解，总体而言，这可能在未来研究中为鉴定AD敏感的早期生物标志物发挥潜在作用。
