Molecular Mechanisms of Neurodegeneration: Role of Tau Protein Aggregation in Alzheimer’s Disease Using Western Blot and Immunohistochemistry

Abstract

Neurodegenerative disorders, particularly Alzheimer’s disease (AD), are characterized by progressive neuronal loss and cognitive decline, with tau protein aggregation serving as one of the central pathological hallmarks. This review paper explores the molecular mechanisms underlying neurodegeneration with a specific focus on tau protein hyperphosphorylation, misfolding, and aggregation into neurofibrillary tangles. It further highlights how experimental techniques such as Western blotting and immunohistochemistry (IHC) are used to investigate tau pathology in both clinical and preclinical models. Western blot analysis enables quantitative assessment of tau isoforms, phosphorylation states, and aggregation profiles, while immunohistochemistry provides spatial localization of tau deposits within brain tissues, revealing region-specific vulnerability such as the hippocampus and cortex. The study synthesizes current literature on tau-associated signaling pathways, including kinase and phosphatase dysregulation, protein clearance impairment, and neuroinflammatory contributions. Additionally, it discusses how combined application of Western blot and IHC enhances diagnostic accuracy and improves understanding of disease progression. Despite advances, challenges remain in standardization of detection methods, interpretation of tau species heterogeneity, and correlation with clinical severity. Overall, this review emphasizes that integrating biochemical and histopathological approaches provides a more comprehensive understanding of tau-driven neurodegeneration in Alzheimer’s disease.