It now appears likely that soluble oligomers of amyloid-β 1-42 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 Aβ oligomerization and reduce pathogenicity. This study has focused on oleocanthal (OC), a naturallyoccurring phenolic compound found in extra-virgin olive oil. OC increased the immunoreactivity of soluble Aβ species, when assayed with both sequence-and conformation-specific Aβ 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 (Aβ-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.

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Although numerous biochemical and physiological differences have been shown to be correlated with alcohol preference, less is known about behavioral factors that may correlate with alcohol preference. Using a signaled barpressing task, alcohol-preferring (P; n = 18) and alcohol-nonpreferring (NP; n = 19) rats were compared for their ability to learn an appetitive and an aversive task. Results showed that P rats had difficulty learning the tasks in comparison with NP and nonselected, control rats when appetitive training was given first. However, if aversive training came first, the NP rats performed poorly in comparison with the P and nonselected rats. These results suggest that these lines of rats may differ in behavioral inhibition and sensitivity to conditioned fear. Furthermore, these behavioral differences may offer a richer analysis of the traits that were co-selected with the alcohol-seeking and alcohol-avoiding phenotypes.