How much do genes contribute to developing Alzheimer’s?

By Dr. Helena Popovic, Medical Doctor, International Speaker and leading authority on improving brain function
June 2023

There are two categories of genes related to Alzheimer’s. One category is referred to as deterministic. This means if you inherit the gene, you are guaranteed to get Alzheimer’s — but you can nonetheless delay the onset and slow progression through brain-healthy choices. We know of three genes in this category. They are called:

1. Presenilin 1 (PSEN1)
2. Presenilin 2 (PSEN2)
3. Amyloid precursor protein (APP)

If either of your parents carries one of these genes, there’s a 50% chance the affected parent will pass the gene to you. Fortunately, these genes are very rare and account for less than 1% of Alzheimer’s cases worldwide.

The second category of genes is referred to as risk factor genes. If you inherit a risk factor gene, you are more prone to getting Alzheimer’s than someone without the gene — but you are by no means destined for the disease. The best known Alzheimer’s risk factor gene is APOE4. If you inherit one copy of this gene from a parent, you have a two to four-fold higher risk of Alzheimer’s than someone without this gene. If you inherit two copies of APOE4, you are eight to 10 times more likely to get Alzheimer’s. In November 2022, Chris Hemsworth announced that he was taking a break from acting to reassess his personal priorities after discovering that he had two copies of the APOE4 gene.

However, ethnicity plays a significant role in how the APOE4 gene affects brain health. People with APOE4 who are Nigerian, Hispanic or Latino are much less likely to develop Alzheimer’s than E4 carriers of Caucasian or Japanese decent. Hence, a single gene never tells the whole story. A person’s risk of Alzheimer’s is very much influenced by other genes they’ve inherited along with their APOE4. In other words, the APOE4 behaves differently depending on its neighbouring genes. Many people with the APOE4 gene never develop Alzheimer’s because somewhere in their DNA they also carry protective genes or they lead a healthy lifestyle.

Most genes have on-off switches or at least dimmer switches that are influenced by what we eat, how much we exercise, the quality of our sleep, how we manage stress, the toxins we’re exposed to and what we believe.

The critical message is that our genes do NOT determine our destiny. Carriers of the APOE4 gene who have a positive view of ageing do not develop Alzheimer’s at a higher rate than non-carriers. In other words, an optimistic view of ageing cancels out the negative effects of the APOE4 gene! Likewise, people with two copies of the APOE4 gene nullify their increased risk if they engage in daily (or almost daily) physical exercise. In contrast, if an APOE4 carrier develops type 2 diabetes, their risk of Alzheimer’s skyrockets. Several studies have also found that APOE4 carriers are less able to to get away with smoking, sustaining a head injury and drinking alcohol. As little as a few drinks a month appears to be detrimental to the brain of an APOE4 carrier.

To date, hundreds of genes have been found to influence the risk of a person developing Alzheimer’s — some increase the risk, others reduce it. The message is to make the healthiest choices we can, as often as we can, and to realise that our decisions are more powerful than our DNA.

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