I have APOE4 -- how serious is that, and what can I do about it?

APOE4 is the best-known genetic risk factor for late-onset Alzheimer's disease. Even one copy raises your risk considerably and lowers the average age at which the disease begins. With two copies, the risk climbs to around 90% before the age of eighty, with an average onset age of 68. That said, even with one copy a diagnosis is by no means inevitable.

The gene acts through several pathways at once. It disrupts the clearance of amyloid-beta (a harmful protein that accumulates in the brain), promotes the build-up of tau proteins, impairs cholesterol transport and energy metabolism in the brain, and even disrupts sleep. This damage begins around twenty years before the first symptoms appear. APOE4 also raises the risk of cardiovascular disease and stroke, although the extent of that risk varies by sex and ethnicity.

There is good news: modifiable lifestyle factors sometimes carry more weight than the gene itself. In a large cohort study using the UK Biobank (more than 5,600 participants), having high blood pressure or diabetes before the age of 62 conferred a greater Alzheimer's risk than APOE4 alone. Obesity before age 62 increased the risk by 54%. Between ages 62 and 72 the risk nearly tripled. Only after age 72 did APOE4 become the dominant factor. Early intervention on blood pressure, blood sugar, and weight is therefore concretely worthwhile.

On the nutrition front, there is an initial positive signal. In a prospective Harvard cohort study, a Mediterranean diet influenced dementia-related markers in the blood more favourably in people with two copies of APOE4 than in non-carriers. This suggests that diet may be especially relevant for APOE4 carriers. Evidence that it actually prevents dementia is still lacking. The idea that the stomach bacterium Helicobacter pylori increases risk in APOE4 carriers was not confirmed in a large Norwegian cohort study.

Specific preventive medications for APOE4 carriers are still under development. For now, the greatest benefit comes from lifestyle: keep blood pressure, blood sugar, and weight under control as early as possible, and consider a Mediterranean dietary pattern. Discuss your individual situation with a doctor or genetic counsellor so that the approach can be properly tailored to your personal circumstances.