Alzheimer’s-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal

This study of Pitt et al. has focused on oleocanthal (OC), as a compound capable of altering the assembly state of soluble oligomers of amyloid-β1-42 peptide (ADDL), which peptide is a neurotoxin that causes Alzheimer’s disease (AD). OC increased the immunoreactivity of soluble Aβ species, indicating changes in oligomer structure. Analysis of oligomers in the presence of OC showed an upward shift in molecular weight and a ladder-like distribution of SDS-stable ADDL subspecies.

In comparison with control ADDLs, oligomers formed in the presence of OC (Aβ-OC) showed equivalent co-localization 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.

Oleocanthal protects the neurons from the negative effects of Alzheimer's disease even at low doses and as a result in the future it could be used in a potential therapy.

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