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

Drive with Dr. Peter Attia

Podcast Notes Key Takeaways The brain is an electrical system that uses lipids to facilitate firing but uses glucose for energyThe brain prefers glucose as the predominant source of energy via GLUT1; the rest of the body uses GLUT4 (insulin-regulated transporter)The brain does its best to regulate glucose content, not dependent on insulin signalingWhen glucose is not available, the brain extracts all ketone bodies from fatty acids outside the brain to maintain itself  Historically, ApoE4 was associated with better outcomes prenatally and against parasite and disease – that changed as more movement, interbreeding, and dietary challenges took place“If you have two copies of ApoE4, your chance of getting Alzheimer’s disease increases 12-fold. If you have one copy of ApoE4 your chance of getting Alzheimer’s increase 2-4 fold” – Dr. Hussein YassineUnlike ApoA or ApoB you can’t make an assumption about the function of ApoE based on its concentrationAncestral diets rich with meat supported richness of ApoE4 – moving to a plant-based diet, increase in carbs supported ApoE 2 and ApoE 3 because they support GLUT1 expressionWe rely on diet to get omega-3s: the human body doesn’t have an efficient system to make EPA and DHA“Omega-3 fatty acids are important for the brain, we can’t make them efficiently, and we’re not consuming enough of them.” – Dr. Hussein YassineThere isn’t enough evidence to suggest supplementing with omega-3s but there is enough to suggest eating one serving of fatty fish per week

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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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Show notes page for this episode: https://peterattiamd.com/HusseinYassine 

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