Role of β-Amyloid Aggregates in Alzheimer’s Disease Pathogenesis:Investigation of Amyloid-β Levels via Western Blot Analysis

Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder worldwide, is characterized by progressive cognitive decline and extensive neuronal loss. A central pathological hallmark of AD is the accumulation of β-amyloid (Aβ) peptides, particularly Aβ_40 and Aβ_42, in the brain, forming extracellular plaques that are considered pivotal in initiating a cascade of neurotoxic events. This study aims to elucidate the role of Aβ aggregates in the pathogenesis of AD, with a specific focus on the quantification and molecular profiling of amyloid-β species using Western blot analysis. By examining post-mortem human brain tissues from AD patients and age-matched non-demented controls, we assessed the levels, solubility, and aggregation states of Aβ peptides in both soluble and insoluble fractions. Western blotting allowed the resolution of distinct Aβ forms, including monomers, oligomers, and high molecular weight aggregates. We observed a marked elevation of oligomeric Aβ species in AD brains, correlating with tau pathology and synaptic protein loss, underscoring their role in synaptic dysfunction and neuronal degeneration.Our findings reinforce the amyloid cascade hypothesis, suggesting that soluble Aβ oligomers may be more neurotoxic than mature fibrils or plaques.