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ApoE4s, your Genes Aren’t Your Fate

Alzheimer’s disease is perhaps the scariest of all human diseases. It not only steals your memories and personality, it steals your friends, family, and self. For those who love you, it’s a tortuous and long goodbye.

Since the ApoE4 gene is the main genetic risk factor for Alzheimer’s disease, discovering you have ApoE4 in your DNA is akin to finding rat feces in your genetic happy meal.

(ApoE4 is thought to confer a 3-15-fold increased risk for Alzheimer’s, depending on whether you have one or two copies; 25% of people have one copy and 2% of people have two copies.)

But the conclusion to this story isn’t written, and it remains to be determined whether this tale is a horror for those who lost the genetic lottery, or a thriller with a happy ending.

Exciting new research suggests that there is a lot ApoE4s can do to massively reduce their risk of developing Alzheimer’s disease. The study in question was published in November of 2019 in The Journal of Gerontology and was entitled, “Varying Effects of APOE Alleles on Extreme Longevity in European Ethnicities.”

For this study, the researchers harvested ApoE genetic data from several different healthy-aging databases and searched for categories of people who lived into the oldest 1% of the population.

While living to be older than 95 years old for men and 99 years old for women doesn’t necessarily imply a life without Alzheimer’s disease, it’s actually a very good proxy. That is because while Alzheimer’s is an aging disease, its prevalence peaks at around 85, and then actually drops. The theory goes that those who live beyond 85 have proven themselves to be so healthy that it’s less likely they will develop Alzheimer’s (which is not a part of normal healthy aging).

But, back to the study. By analyzing the genetic data of 2,143 extremely long-lived people, and 6,825 shorter-lived controls, the researchers discovered that the impact of the ApoE4 allele on longevity varied based on ethnicity. Specifically, ApoE4 did not appear to significantly impact the risk of developing Alzheimer’s disease in Southern Italians.

For those of you who like statistics, here are some numbers: The odds ratio for the impact of ApoE4 on extreme longevity runs at around 0.3 - 0.5. This means you are less likely to live to be really old if you have ApoE4. However, in the Southern Italians, the same odds ratio was 0.82!

Basically, on the surface, people with Southern Italian heritage appeared resistant to the negative longevity effects of ApoE4. But, like any good thriller, there remains a twist that you didn’t expect…

When the researchers partitioned Southern Italians into those who lived in America and those who lived in Italy, they noted a stark division: Italian-Americans carrying the ApoE4 were actually at an elevated risk of early death (odds ratio = 0.19), whereas the Italians living in Italy fared even better than the initial analysis suggested (odds ratio = 1.21, CI: 0.79 – 1.85).

What does this mean? This means that the genetics of the Southern Italians probably isn’t the main factor protecting them from ApoE4, dying young, and, presumably, Alzheimer’s disease. Rather, environmental factors associated with the Southern Italian way of life, like their Mediterranean diet, may be what is protecting them.

The numbers may not mean that much to a lot of you. But the fact that odds ratio for extreme longevity in Italian ApoE4 carriers who live in America is 0.19, whereas it’s 1.21 for those who live in Italy, is a huge deal! It supports the notion that, by adjusting our lifestyles, we truly can influence our risk of developing Alzheimer’s disease.

In other words, your genes load the gun, but environment pulls the trigger… nurture over nature… DNA isn’t fate… the choices you make matter!


No medical advice

The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.


So, what actions would we recommend (unofficially, without being medical advice) for those who carry the ApoE4 gene? Well, it all starts with nutrition. It’s likely best to eat a diet devoid of refined sugar, carbohydrates, and processed foods, and a diet rich in organic meats or small fatty fish (like sardines), avocados, olive oil and olives, and colorful vegetables. On top of that, sleep is critical; try to reduce stress (try yoga and meditation); and get regular physical activity. Social relationships are also important to good health, and there’s some interesting data on saunas decreasing the risk of Alzheimer’s disease by activating a class of proteins called heat shock proteins (you can find more information on in one of our previous posts).



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