Evaluation of oral oleocanthal to prevent and/or treat Alzheimer's disease and related dementias

PROJECT SUMMARY Alzheimer s diseaseADis a progressive neurodegenerative disorder of the elderly that afflicts aboutmillion patients globally and overmillion Americans in the USDespite the considerable research effort to preventtreator cure the diseaseeffective strategies remain lackingThe accumulation of amyloidAin the brain blood vessels can result in the development of cerebral amyloid angiopathyCAACAA is a pathological feature present concomitantly with AD at a high frequencyhighlighting a potentially important role for vascular Ain dementias such as ADCurrently no treatment is available to slow or stop the progression of CAA and ADThe purpose of this application is to evaluate oleocanthalOCa natural phenolic compound isolated from extra virgin olive oilas a novel molecule with neuroprotective effects against AD in a mouse modelThe overall goal of this project is to generate data to inform the commercialization pathways Oleolive will follow for OC and guide the company development strategy to be proposed in a Phase II SBIRThe central hypothesis is that low dose nano emulsions of OC in water fed to mice will be effective as a preventive and therapeutic in mouse models of ADThis hypothesis will be tested by pursuing the following specific aimsAimPerform dose dependent studies to determine the optimum protective dose of orally administered OCThis Aim will be examined via the Sub Aimsaevaluate OC effect on BBB integrityvascular and cerebral Aloadand synaptic integrityand bevaluate OC effect on efficacy and toxicity biomarkersAimEvaluate the effect of orally administered OC on metabolic and behavior phenotypesMethods and techniques to be used to accomplish the above aims include in vivo studies in AD mouse modelbiochemical analysismicrovessels isolation from mice brainstoxicity and histopathology studiesand metabolic and behavior phenotype studiesFindings from this work are expected to confirm OC as a novel molecule to prevent and or treat AD and related dementias and would support and advance OC therapeutic development toward clinical trials NARRATIVE AD and AD related dementiasADRDconstitute a major public health problem and have been reported to triple healthcare costsPreliminary studies show oleocanthal demonstrates promising effects against ADThe proposed project will determine the optimal dose of oleocanthal for safety and efficacy in an AD mouse modeland position oleocanthal as a potential preventive and or treatment for AD and ADRD