Transcriptomic Analysis of Alzheimer's Disease Pathways in a Pakistani Population

• Published in: JAD reports Vol. 8; no. 1; pp. 479 - 493
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: pathogenesis; amyloid processing; Alzheimer’s disease; transcriptomic; gene expression
• ISSN: 2542-4823
• DOI: 10.3233/ADR-230146

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.