#147 - Hussein Yassine, M.D.: Deep dive into the “Alzheimer’s gene” (APOE), brain health, and omega-3s

The Peter Attia Drive

Hussein Yassine is a physician and researcher who studies brain lipid utilization in the context of finding preventative measures for cognitive impairment, specifically Alzheimer’s disease (AD). In my conversation with Hussein, we begin with a fundamental coursework in brain biology—including its architecture and energy systems. We go on to discuss what these systems look like when something goes wrong and cognitive decline ensues. We talk about the evolutionary origins of the ApoE genotype, with specific attention to the ApoE4 allele and its association with AD. We spend time discussing ApoE4 implications for the brain’s fuel utilization, notably omega-3 fatty acids: EPA and DHA. We briefly pivot to the implications of recent omega-3 trials for cardiovascular disease and return to what we currently understand about EPA/DHA and brain health; we contemplate potential dietary interventions across the lifespan to preserve and prolong cognitive function.

We discuss:

• Hussein’s Background and introduction to brain composition (3:00);
• The blood-brain barrier and brain filtration (8:00);
• Lipids and brain function (13:00);
• How the brain utilizes energy (18:00);
• Apolipoprotein E (ApoE) structure and function in the periphery (27:30);
• ApoE function in the brain (38:15);
• Evolutionary origins of ApoE isoforms (43:45);
• ApoE4 variant and Alzheimer’s disease (AD) risk (53:30);
• Dietary fuel preference with the ApoE4 allele (1:03:00);
• The role of omega-3 fatty acids in the brain (1:13:30);
• Comparing findings from the REDUCE-IT and STRENGTH trial (1:21:45):
• The relationship between dietary omega-3 intake and brain health (1:34:15);
• Preventing cognitive decline: A critical window for DHA in ApoE4 carriers? (1:42:30);
• Hussein’s ongoing research and recommendations for E4 carriers (1:54:00); and
• More.

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