What ApoE4 Carriers Need To Know About A New Study

Rethinking the impact of this Alzheimer’s risk gene

Hello, everyone. A study about ApoE4 and Alzheimer’s was published in the journal Nature this week and many of you have contacted me with questions. The researchers provide a novel perspective about the role of the Alzheimer’s risk gene ApoE4. It’s creating a lot of buzz because they postulate that carrying two copies of ApoE4 should be considered a genetic form of the disease. It’s natural for studies like this to generate the kind of scary headlines that fuel fears about getting Alzheimer’s. This study, as you will see, looks at Alzheimer’s through the lens of biomarkers, not clinical symptoms. We’ll go into why this matters, below.

If you are an ApoE4 carrier, I know how distressing news like this can be. Before we go any further, please know that carrying one or two copies of the gene does not guarantee you will develop Alzheimer’s disease. All that we’ve learned about turning these genes off still holds true. Nutrition, exercise, and environmental factors determine whether or not the ApoE4 gene becomes problematic. 

For today’s newsletter, I was going to share a few favorite recipes from the new cookbook Food of Sicily. Instead, I think it’s important that we take a deep look at the study published on May 6 in the journal Nature Medicine: APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease.

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6 Facts About ApoE4 

What it is: ApoE is a gene that has evolved over time to have three different variants, called alleles: ApoE2, ApoE3, and ApoE4. Everyone inherits one ApoE allele from each parent. You could have an ApoE2 and an ApoE3, for instance, or a combination of ApoE3 and ApoE4. Carrying one copy of ApoE4 increases the risk of developing Alzheimer’s later in life by three- to five-fold; having two copies increases risk tenfold, and some studies say up to fifteen-fold. 

What it does: While ApoE4 is known as an Alzheimer’s risk gene, it exerts its effect on the brain indirectly by how it moves blood cholesterol into cells. A glitch in the gene’s structure creates a faulty transport mechanism. The brain cells bear the brunt of the problem, getting too much of the type of cholesterol known to cause damage to blood vessels (LDL) and not enough docosahexaenoic acid (DHA)—the brain-repairing omega-3 fatty acid. This, in turn, affects processing or production of beta-amyloid and tau, proteins that damage the brain over time and are sometimes associated with Alzheimer’s dementia.

ApoE4 is common: Twenty-five percent of all Americans carry one copy of ApoE4; two percent carry two copies. 

ApoE4 gets expressed differently depending on these factors: Race (white people express it more than blacks and Latino people, for instance); sex (women express it more than men); where you live (Southern Italians who carry two ApoE4s and live in the U.S. are more likely to develop Alzheimer’s than if they live in Southern Italy where their risk is the same as if they didn’t carry the genes).