#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

ApoE's Role in Periphery

Apolipoprotein E (ApoE) in the periphery acts as a conductor, regulating lipoprotein metabolism and clearance.
Unlike ApoB or ApoA1, ApoE is promiscuous, associating with various lipoproteins like HDL, LDL, IDL, and VLDL.

INSIGHT

ApoE's Role in Brain

In the brain, ApoE supports astrocytes, facilitates lipid transport between cells, and plays a role in repair after injury.
It also regulates inflammation and escapes lysosomal degradation, unlike ApoB.

INSIGHT

Evolutionary Perspective of ApoE4

ApoE4, the ancestral variant, likely conferred survival advantages in infection-prone environments by enhancing the inflammatory response.
Its link to Alzheimer's disease may be due to increased lifespan and changes in environment and diet.

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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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