Oleanolic Acid and Alzheimer’s Disease: Mechanistic Hypothesis of Therapeutic Potential

Abstract

Numerous hypotheses have been proposed to explain the origin of Alzheimer’s disease (AD), a chronic neurodegenerative disorder that currently has no curative treatment. These hypotheses include the abnormal accumulation of β-amyloid and hyperphosphorylated Tau, degeneration of cholinergic neurons associated with chronic neuroinflammation and oxidative stress, and dysregulation of lipid and carbohydrate metabolism. oleanolic acid (OA), a pentacyclic triterpenoid widely distributed across plant species, has demonstrated anti-inflammatory and antioxidant activities, anti-aggregation properties, together with regulatory effects on carbohydrate and lipid metabolism. Given the diversity of hypotheses proposed for AD and its multifactorial nature, the pleiotropic actions of OA positions it as a promising candidate for preventive and therapeutic strategies. This review compiles evidence on OA and selected synthetic derivatives, analyzing their impact across the major mechanistic hypotheses of AD pathogenesis. Collectively, these findings support OA as a promising candidate to address protein aggregation, metabolic imbalance, and neuroinflammation in AD.