Most blood tests give a result that can change: cholesterol goes up and down, blood sugar shifts with habits. The ApoE genotype test is different. It reads part of your DNA, so the answer is the same at 30 as at 70. That makes it a test you usually only do once, and one that is worth thinking about before ordering.
This article explains what the APOE gene does, how its common versions relate to cholesterol and cardiovascular risk, what it can say about Alzheimer's disease, and what to weigh up first.
What apolipoprotein E does
Apolipoprotein E, or ApoE, is a protein made mainly in the liver. A review in Pathology describes its central job: it attaches to triglyceride-rich particles in the blood and helps the liver clear their "remnants" once their fat has been used (Marais, 2019). It also works in the nervous system, where it helps move fats between cells.
The gene that carries the instructions for this protein, APOE, comes in three common versions, called alleles: E2, E3 and E4. Everyone inherits one copy from each parent, so a person's genotype is a pair, such as E3/E3 or E3/E4.
What the ApoE genotype test shows
The Apolipoprotein E genotype test in the BPR Clinic catalogue identifies which two of these alleles you carry. According to the LML, which processes the test:
- E3 is the most common allele and is considered neutral for cardiovascular risk;
- E4 is associated with a higher risk of atherosclerosis and coronary artery disease;
- E2 is considered to have a protective effect in most people.
The review in Pathology adds that these versions account for much of the natural variation in blood lipids, with E2 generally the most favourable and E4 the least favourable for cardiovascular and neurological health (Marais, 2019).
The exception with E2
There is a twist. People with two copies of E2 (E2/E2) can, in the presence of other risk factors or metabolic stress, develop a lipid disorder called dysbetalipoproteinaemia, in which remnant particles build up in the blood (Khalil et al., 2021). This is one of the situations where professionals find the genotype most useful: it helps explain an unusual cholesterol and triglyceride pattern.
The Alzheimer's question
This is the part people most often do not expect. The same gene is also the strongest common genetic risk factor for Alzheimer's disease. A review in Molecular Neurodegeneration explains that the E4 allele significantly increases risk, while E2 is protective compared with E3 (Raulin et al., 2022). The LML notes the same link, particularly for late-onset cases.
Two points help keep this in proportion:
- carrying E4 raises risk but does not mean someone will develop the condition, and the condition also occurs in people without E4;
- the NHS notes that age is the single most significant risk factor for Alzheimer's disease, and that the increase in risk from inherited genes is, for most people, small.
Even so, a result like this cannot be unlearned. If you order the test for cholesterol reasons, you will also receive information that relates to dementia risk.
What to consider before ordering
The NHS describes genetic counselling as a way to think through what a genetic test means for you and your family before having it. Some useful questions:
- What would I do differently with the result?
- How would I feel about learning I carry one or two copies of E4?
- Do I want relatives to know? Because genes are shared, a result can say something about parents, brothers, sisters and children.
The LML asks for clinical history to be provided with this test. That is one more reason to discuss it with a healthcare professional first, who can also help you read the result alongside your lipid profile.
