The PreventE4 study: testing omega-3 supplementation in APOE4 carriers before the onset of dementia

The APOE4 gene is the strongest genetic risk factor for Alzheimer’s disease (AD). One feature of the APOE4 brain is its ability to modulate the metabolism of fatty acids, specifically polyunsaturated fatty acids. A recent trial of brain delivery of supplemental docosahexaenoic acid (DHA) in patients with AD risk factors found that the increase in omega-3s in the brains of participants with the APOE4 gene was significantly lower than those without it, suggesting the APOE4 system consumes more omega-3s than APOE2 or APOE3, or that it is not absorbed into the brain as efficiently. Hussein Yassine, MD, Keck School of Medicine, University of Southern California, Los Angeles, CA, discusses the aims and expected outcomes of the PreventE4 study (NCT03613844): a Phase II double-blind, randomized clinical trial examining whether high dose omega-3 supplements (in the form of DHA) can prevent AD onset in high risk APOE4 carriers. The study will primarily assess the levels of omega-3s in the brain to test if high dose DHA supplementation is efficient in enriching the brain with omega-3s. This interview took place at the Clinical Trials on Alzheimer’s Disease Congress 2022 in San Francisco.

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