INTEGRATIVE SYSTEMS BIOLOGY AND MULTI-OMICS APPROACHES IN ALZHEIMER'S DISEASE: BRIDGING BIOMARKERS, NEUROINFLAMMATION, AND PRECISION MEDICINE

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a gradual decline in cognitive function, driven by synaptic dysfunction and neuronal loss, particularly in the hippocampus a region critical for memory and learning. A hallmark of AD pathogenesis is the aggregation of amyloid-beta (Aβ) peptides into toxic oligomers, which initiate a cascade of events leading to amyloid plaque formation, activation of reactive microglia and astrocytes and subsequent neuronal damage. Neuroinflammation and oxidative stress plays pivotal roles in AD progression, with the interplay between these processes exacerbating the pathological features of the disease. Pro-inflammatory signaling pathways activated by reactive immune cells and the excessive production of reactive oxygen species (ROS) disrupt cellular homeostasis, further accelerating neurodegeneration. This review delves into the intricate mechanisms linking Aβ pathology with inflammatory and oxidative stress responses and highlights how multi-omics and neuroimaging enable precision medicine through molecular and structural brain correlation. Recent advances in understanding the molecular pathways have unveiled potential biomarkers that hold promise for improving diagnostic precision and monitoring disease progression. Furthermore, this review highlights novel therapeutic strategies identified through systems biology approaches, emphasizing their potential to target the multifaceted nature of AD pathophysiology. By exploring the nexus of amyloid pathology, neuroinflammation and oxidative stress, this work aims to provide a comprehensive framework for developing targeted interventions that may mitigate the burden of this devastating disease. This review critically evaluates network-based analyses and case studies in genomics, proteomics and metabolomics that have identified candidate biomarkers and therapeutic targets in AD.