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

Feb 1, 2021

Hussein Yassine, an Associate Professor at USC, discusses the challenges of Alzheimer's disease and the pivotal role of the APOE gene, especially the APOE4 variant. He breaks down the relationship between omega-3 fatty acids and brain health, explaining how EPA and DHA impact cognitive function. The conversation includes insights into brain metabolism and lipid utilization, as well as dietary strategies for those at risk. Yassine highlights the need for early lifestyle interventions to protect cognitive health as we age.

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INSIGHT

Brain's Primary Function

The brain, unlike other organs, prioritizes electrical signal transduction over functions like contraction or filtration.
This explains its high lipid content, crucial for myelin sheaths and synapses, optimizing signal transmission.

INSIGHT

Brain Lipids and Signaling

The brain's lipid-rich composition is tied to its reliance on electrical signaling for function.
Lipids form specialized structures like myelin and synaptosomes, facilitating rapid signal transduction.

INSIGHT

Brain Energy Utilization

The brain primarily uses glucose for energy, regulated by GLUT1 transporters, not insulin-dependent GLUT4.
In glucose scarcity, the brain efficiently uses ketone bodies, while fat is mainly for structural components.

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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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