Oleuropein-Rich Olive Leaf Extract Attenuates Neuroinflammation in the Alzheimer's Disease Mouse Model

Alzheimer's disease (AD) is the most common form of dementia among several neurodegenerative disorders afflicting the elderly. AD is characterized by the deposition of extracellular amyloid-β (Aβ) plaques, disrupted blood-brain barrier (BBB), and neuroinflammation. Several studies have demonstrated the health benefits of olive oil and olive leaf extract (OLE) due to their polyphenolic content. The main phenolic compound in OLE is glycosylated oleuropein (OLG), while the aglycon form of oleuropein (OLA) exists in much lower amounts. This work aimed to evaluate the effect of a low dose of OLG-rich OLE and the mechanism(s) that contributed to the observed beneficial effects against Aβ pathology in the homozygous 5xFAD mouse model. Mice were fed with OLE-enriched diet (695 μg/kg body weight/day) for 3 months, starting at 3 months old. Overall findings demonstrated that OLE reduced neuroinflammation by inhibiting the NF-κB pathway and suppressing the activation of NLRP3 inflammasomes and RAGE/HMGB1 pathways. In addition, OLE reduced total Aβ brain levels due to increased clearance and reduced production of Aβ and enhanced BBB integrity and function, which collectively improved the memory function. Thus, the consumption of OLE as a dietary supplement is expected to stop and/or slow the progression of AD.