Olive oil compound – a key to stopping Alzheimer’s?
Many people are aware of the heart-promoting aspects of olive oil. It is a source of healthy fats that help build blood vessels, it provides compounds that help regulate blood pressure, and it is a strong antioxidant that prevents free radical damage. However, what may come as a surprise is that olive oil also contains a compound called oleocanthal, which has been the focus of intensive research in recent years.
This phenolic compound interrupts the cycle of the plaque formation in the brain. As the building blocks of plaques assemble between the cells in the brain, they block neuronal signals, and interfere with memory and recall. But oleocanthal changed the mechanics of amyloid beta plaque formation, and appeared to protect nerve pathways of the brain.
Pitt J, Roth W, Lacor P, et al. Alzheimer's-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicology and Applied Pharmacology 2009; 240: 189-197.
It now appears likely that soluble oligomers of amyloid-beta1-42 peptide, rather than insoluble fibrils, act as the primary neurotoxin in Alzheimer's disease (AD). Consequently, compounds capable of altering the assembly state of these oligomers (referred to as ADDLs) may have potential for AD therapeutics. Phenolic compounds are of particular interest for their ability to disrupt Abeta oligomerization and reduce pathogenicity. This study has focused on oleocanthal (OC), a naturally-occurring phenolic compound found in extra-virgin olive oil. OC increased the immunoreactivity of soluble Abeta species, when assayed with both sequence- and conformation-specific Abeta antibodies, indicating changes in oligomer structure. Analysis of oligomers in the presence of OC showed an upward shift in MW and a ladder-like distribution of SDS-stable ADDL subspecies. In comparison with control ADDLs, oligomers formed in the presence of OC (Abeta-OC) showed equivalent colocalization at synapses but exhibited greater immunofluorescence as a result of increased antibody recognition. The enhanced signal at synapses was not due to increased synaptic binding, as direct detection of fluorescently-labeled ADDLs showed an overall reduction in ADDL signal in the presence of OC. Decreased binding to synapses was accompanied by significantly less synaptic deterioration assayed by drebrin loss. Additionally, treatment with OC improved antibody clearance of ADDLs. These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics.