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What If You Could Prevent Alzheimer’s?

GENETIC KEYBOARD

What if—in your 20s, 30s, or 40s—you could stop yourself from ever getting Alzheimer’s? One filmmaker says it’s possible.

The Human Genome Project was an international scientific research project with the goal of determining the entire sequence of chemical base pairs (represented by the letters A, G, C, and T) that make up human DNA. Many scientists believed at the time that genetic predisposition was the heart and soul of human disease, and thus the key to understanding how to cure many of them. By unraveling and decoding the human genome, we’d solve at least some of humanity’s largest health woes.

The moonshot project continues to be a marvel of human ingenuity and certainly paved the way for others to come, most recently the Obama administration’s BRAIN Initiative to map out all of the neurons in the human brain. That we are a species that can read its own DNA could be described as something of a miracle, if only using such a word didn’t undermine the decade-plus of work by the brilliant minds behind it.

There’s only one problem.

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After the completion of the project in 2003, scientists were dumbfounded by how rudimentary the human genome actually is. No one could have anticipated just how few genes it required to make up a human. In fact, some lesser animals have more genes than the roughly 23,000 that make us us. Our genetic complexity puts us in the same range as mice. Even the water flea has more genes than us. Humbling, to say the least.

But while the Human Genome Project might have been a bit of a letdown in that regard, it did give rise to what had previously been an inconceivable notion: That environmental factors might switch on and off certain genes, thus accounting for the wide array of diversity among humans despite relatively little genetic variation (0.1 percent, to be specific). For the first time, our lives weren’t dictated exclusively by what we owed to nature and to nurture. The brave new world of “epigenetics” alluded to the fact that our destinies may be a combination of both, and that we may have agency in how the latter affects the former.

I recently interviewed Dr. Alessio Fasano, director of the Center for Celiac Research at Massachusetts General Hospital, who summed up the value of epigenetics with a metaphor that anyone who appreciates music will enjoy. If you think of your genome as a keyboard with roughly 23,000 notes, there are certainly notes on that keyboard that can play the songs “Cardiovascular Disease,” “Rheumatoid Arthritis,” or even “Alzheimer’s Disease,” just like any keyboard can play Mozart’s Sonata in C, though few of us can influence one to do so. The power of epigenetics lies in being able to influence the song being played by our genetic keyboards.

“If you understand the intricacy of this epigenetic concept, you can intervene,” Fasano told me. While some of us may have genetic risk factors for any number of maladies, we might be able to live our lives in a way that minimizes the risk that these songs will be played.

Some interesting research in recent years provides insight into how we may do just that.

One study published in 2008 showed that exposing the brains of mice to as little as six hours of high blood sugar led to epigenetic changes that increased risk of vascular damage. These changes lasted even after six days of normal blood glucose, representing long-term damage after just a short sugar spike.

Another study, published in the Journal of Nutrition, Health and Aging in 2010, found that higher blood sugar was associated with prematurely shorter telomere length (telomeres being the “shoelace tips” that protect chromosomal integrity and shorten with age) and damage to its associated DNA. These are startling but empowering insights certainly worthy of further investigation, and, if true for humans, might make us rethink more carbohydrate-rich indulgences.

Finally, Vitamin D, the sunshine hormone, influences about 1,000 genes involved in important functions like regulating cell growth, modulating immune function, and maintaining cardiovascular health. Three-quarters of U.S. teens and adults are deficient in Vitamin D, according to 2009 research, with the highest rates seen in blacks, followed by Hispanics. Does this mean that three-quarters of the U.S. population could be stunting the expression of nearly 5 percent of their genome? It would be an unfortunate yet easily remedied proposition.

In my new documentary project Bread Head, I will investigate the interplay between our lifestyles, diets, and genes as it pertains to the health of our brains. I want to explore the notion that America’s most feared disease—Alzheimer’s—currently reaching epidemic proportions in the US, may not befall us by a game of genetic Russian roulette, but due—at least for some of the 45 million people worldwide suffering from it—to factors that we might be able to influence. Just like our genes.

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