An excerpt from The Invincible Brain: The Clinically Proven Plan to Age-Proof Your Brain and Stay Sharp for Life by Majid Fotuhi. Copyright © 2026 by Majid Fotuhi. From Harper Wave, an imprint of HarperCollins Publishers. Reprinted by permission.

Your brain is constantly changing. While the primary structures remain the same, you can grow and shrink your cortex and hippocampus according to what you do. But what about genetics? You cannot change that, right? Your DNA is your DNA, so to what extent is your brain a victim (or victor) of its genetic destiny?

It is easy to say, and worry, about genetics, especially since almost anyone can do a cheek swab or spit in a tube to get a genetic portrait. Knowing what genetic variations you have and what disease risks correlate with them can be interesting, but it can also be frightening and defeating because it seems so set in stone. People often say, “Heart disease runs in my family,” or “Obesity is in my genes,” or “My grandmother had Alzheimer’s, so I will probably get it, too.”

Take heart! While it is true that many genes and their variants can increase susceptibility to certain conditions, it is simply not true that your genetics equal your health destiny. Genes play only a small to moderate role (depending on the condition) in most common health conditions, including the most common type of dementia, late-onset Alzheimer’s disease.

The power of epigenetics and methylation

The problem is that people often think genetics is all there is to it. If they have a gene that codes for a process that increases risk, they believe they will be doomed to get that disease. In reality, it is not so simple. There are typically many gene variants that can increase or decrease the risks associated with most chronic diseases, and they may cancel each other out or build on each other.

Even more important, though, is that how you live your life and the choices you make can determine whether these genes get activated or not, whether they get “turned on” (expressed) or “turned off” (suppressed). Epigenetics is the interaction between genetics and lifestyle.

One of the most important epigenetic processes is methylation, which influences whether genes are expressed or suppressed. Methylation affects the synthesis of proteins involved in essential cellular functions such as generating ATP for energy, producing brain-derived neurotrophic factor (BDNF), reducing inflammation, building structures, and regulating growth and development.

BDNF, in particular, is a critical protein for the brain. It helps to support the survival of existing neurons, promotes the growth of new neurons and synapses, and is involved in neuroplasticity. It is vital for learning, memory, overall cognitive function, and the prevention of Alzheimer’s disease. Lifestyle factors such as poor sleep and prolonged stress can add methyl groups to the DNA gene that codes for this critical protein, reducing BDNF production. Fortunately, positive lifestyle choices such as exercise, eating a heart-healthy diet rich in omega-3 fatty acids, and challenging your brain mitigate this effect and increase levels of BDNF in the brain.

Outsmarting the epigenetic clock

Your genes get turned on and off all the time, according to your body’s needs. Usually, this is a tightly regulated process. Your body plays your genes like a piano, and everything works in concert. Sometimes, however, we get in the way of this natural process by living a lifestyle that interferes with a balanced and healthy methylation level. Poor lifestyle choices and environmental factors, from pollution to a high-sugar diet to too much stress, can trigger hypermethylation via inflammation in ways that increase the risk of health problems such as cancer or late-life Alzheimer’s disease.

Methylation is also closely correlated to aging, so closely associated that some researchers use methylation patterns to estimate biological or “epigenetic” age. Although you cannot affect how old you are chronologically, you can do something about methylation, so you might be able to outsmart the epigenetic clock.

Positive lifestyle choices can make favorable methylation changes in your DNA. You might be 55, but your epigenetic clock might say you have an epigenetic age of 45, implying that you are likely to live longer than usual. In many ways, your epigenetic age is up to you. For example, one study found that even six weeks of physical exercise resulted in positive epigenetic changes in skeletal muscle cells. Genes are not static, and you can definitely influence this process through your lifestyle choices.

The truth about the Alzheimer’s gene

But what about the notorious “Alzheimer’s gene”? Can you influence it? Yes and no.

We all have two copies of the ApoE gene (Apolipoprotein E). We inherit one from each parent. There are three ApoE variants. ApoE3 is the most common version and does not affect Alzheimer’s risk. However, you might have inherited one or two copies of ApoE2 or ApoE4 alleles.

The ApoE2 allele correlates with a lower-than-average risk of developing Alzheimer’s disease or developing it at an older age (perhaps not until the 90s). In contrast, the ApoE4 allele correlates with a higher-than-average risk of developing Alzheimer’s disease or developing it at a younger age (perhaps in the 60s or 70s).

That can sound scary, especially when you discover that you cannot suppress this gene epigenetically. Not every gene variant is subject to epigenetic effects. The extra risk is there no matter what. But here is the good news: Having one or two copies of the ApoE4 variant does not mean you will get Alzheimer’s disease.

There are countless numbers of people who have one or both copies of ApoE4 who never develop Alzheimer’s disease, even in their 90s. There are also many people with other risk factors who do not have ApoE4 but who develop Alzheimer’s disease. The reality is that obesity, diabetes, insomnia, sleep apnea, and many other issues all increase the risk of developing Alzheimer’s disease as much, if not more, than having a copy of ApoE4, and having all these risk factors together can increase the risk of Alzheimer’s disease 16-fold, which is a much higher contribution than having that one gene variation in ApoE. We need a total paradigm shift in the way we think about cognitive decline with aging and the importance of how our day-to-day habits have a profound impact on the health and vitality of our brain, more so than having ApoE4.

The bottom line is that genetics is about susceptibilities, not destiny. Being susceptible or predisposed to something does not mean it will happen. Every day, with everything you do and every choice you make, you could be influencing the expression or suppression of specific genes that can affect your brain specifically, as well as your health and disease risk. Temporary changes, like occasional dietary indulgence or short periods of high stress, probably do not make much difference in how your genes are methylated and expressed, but significant stressors over the course of years can profoundly affect your gene expression.

Majid Fotuhi is a neurologist and author of The Invincible Brain: The Clinically Proven Plan to Age-Proof Your Brain and Stay Sharp for Life.