What is the ApoE4 gene, and how much does it actually raise your risk of Alzheimer's disease?
The ApoE4 gene — short for Apolipoprotein E gene — is one of the single strongest genetic risk factors for Alzheimer's disease. One copy raises the risk two to three times for males and approximately six-fold for females. Two copies raise the risk ten times for males and fifteen-fold for females, making women with the same genetic profile significantly more vulnerable than men.
What is the ApoE4 gene?
The Apolipoprotein E (ApoE) gene comes in several variants. The E4 variant is the one associated with elevated Alzheimer's risk. Everyone inherits two copies of this gene — one from each parent — so it is possible to carry one or two copies of the E4 variant, with risk scaling sharply upward with each additional copy.
| Copies of ApoE4 | Males | Females |
|---|---|---|
| One copy | 2–3× increased risk | ~6× increased risk |
| Two copies | 10× increased risk | 15× increased risk |
The episode makes a point of stressing that carrying the ApoE4 gene is not a foregone conclusion — it is a risk factor, not a death sentence. The example given is actor Chris Hemsworth, who was publicly tested and found to carry two copies of the gene. His case brought mainstream attention to a gene that most people had never heard of, yet which shapes Alzheimer's risk more dramatically than almost any other known genetic marker.
The sex difference in ApoE4 risk is striking and often under-discussed. A woman carrying two copies of the E4 variant faces a fifteen-fold elevated risk — 50% greater than the already alarming ten-fold risk faced by a man with the same genetic profile. This asymmetry is one reason why Alzheimer's disproportionately affects women. You can hear the full conversation on The Diary Of A CEO with Steven Bartlett on Listenly.
"Having strong legs is by far the most important tool in your toolbox for the prevention of Alzheimer's disease."
— The Diary Of A CEO with Steven BartlettGenetics set the risk level, but the episode makes clear that lifestyle — particularly resistance training — can meaningfully offset even a high-risk genetic profile. The ApoE4 finding is presented not to induce fear but to motivate action: knowing your genetic risk is only useful if it prompts the right preventive behaviours.
See also
The SMART trial took a group of people with mild cognitive impairment and gave them resistance training two to three times per week. They not only preserved their cognitive functions — they enhanced their processing speed, their fluid intelligence, and showed a slowing of grey matter loss.