7‐Keto Cholesterol as a Mediator in Alzheimer's Disease Pathogenesis

Abstract

Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation, tau hyperphosphorylation, and oxidative stress. Recent evidence suggests that oxysterols, particularly 7-ketocholesterol (7-KC) may play a pivotal role in AD pathology by exacerbating neuroinflammatory and oxidative damage. 7-KC, a major non-enzymatic oxidation product of cholesterol, is known to contribute to neurotoxicity through mitochondrial dysfunction, lipid peroxidation, and inflammation. Unlike other oxysterols, 7-KC is highly reactive and has been implicated in cell death pathways relevant to neurodegeneration, including ferroptosis and autophagy dysregulation. Sulphation of 7-KC alter its solubility, bioavailability, and interaction with cellular receptors, potentially amplifying its cytotoxic effects in neuronal and glial cells.