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2015 Grants - Yassine
Does APOE-e4 Genotype Reduce the Delivery of Fish Oil to the Brain?
Hussein N. Yassine, M.D.
University of Southern California
Los Angeles, California
2015 New Investigator Research Grant
Does an Alzheimer’s-related genetic variation reduce the beneficial effects of fish oil on brain health?
One of the established risk factors for Alzheimer’s disease is a genetic variation of the apolipoprotein E gene known as (APOE-ɛ4). However, scientists have not yet identified the exact mechanisms by which APOE-ɛ4 increases dementia risk. Recent studies have shown that mice genetically engineered to carry the human APOE-ɛ4 gene have a defect in the ability to transport a certain molecule called docosahexaenoic acid (DHA) from the blood into the brain. DHA is found in fish oil, and is one of several essential fatty acids that have been shown to boost memory and other cognitive abilities. Moreover, these fatty acids are reduced in the brains of people with Alzheimer’s disease. Such findings suggest that APOE-ɛ4 may promote Alzheimer’s disease, in part, by hindering the beneficial effects of DHA on brain health.
Hussein N. Yassine, M.D., and colleagues have shown that people with the APOE-ɛ4 variation have lower DHA levels in their cerebrospinal fluid (the fluid surrounding the brain) suggesting impaired delivery of DHA from the diet into the brain. To further explore this hypothesis, the research team will administer a fish oil supplement to people with and without the APOE-ɛ4 variation and measure the participants’ DHA levels in the blood and cerebrospinal fluid before and after 6 weeks of treatment. The researchers expect that participants with the APOE-ɛ4 variation will show lower DHA levels in the cerebrospinal fluid revealing a chronic deficiency in brain DHA levels that could impact brain health.
Dr. Yassine’s study could reveal a novel mechanism underlying the increased dementia risk for people with the APOE-ɛ4 genotype — a mechanism that occurs well before clinical symptoms of Alzheimer’s become evident.