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

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Alzheimer's disease (AD) is a growing neurodegenerative disorder, particularly affecting elderly populations globally and increasingly in developing nations like Pakistan.
• Understanding the genetic underpinnings of AD is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

• To characterize key genes, their expression levels, and molecular networks involved in Alzheimer's disease pathogenesis within a Pakistani population.
• To identify potential genetic biomarkers for early AD detection through a pilot case-control study.

Main Methods:

• Employed high-throughput qRT-PCR (TaqMan Low-Density Array) and Affymetrix Arrays for global gene expression profiling in 33 AD patients and controls.
• Utilized Ingenuity Pathway Analysis (IPA) to identify molecular networks and signature genes associated with AD pathogenesis, focusing on amyloid processing and related pathways.

Main Results:

• Confirmed 16 differentially expressed AD-related genes, with significant fold changes in CAPNS2 and CAPN1.
• Observed 61% and 39% of genes were significantly up- and downregulated, respectively, in AD patients compared to controls (p-value < 0.05).
• Identified key pathways including Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling, with top networks related to Neurological Disease and Organismal Injury.

Conclusions:

• The study presents a non-invasive method combining TLDA and global gene expression analysis using whole blood for investigating AD.
• Findings provide valuable insights into gene expression patterns, particularly in Amyloid Processing, suggesting potential for identifying sensitive, early AD biomarkers.