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Increased genetic risk of Alzheimer’s disease due to presence of Apolipoprotein E (E3/E4) variants

In April 2017, the Food and Drug Administration (FDA) approved 23&Me’s Apoe gene test to predict risk of late onset Alzheimer’s disease. This is the first time a direct-to-consumer genetic testing company was given the approval to market the test in the US. The genetic test looks for polymorphisms in a gene called apolipoprotein (ApoE).

According to a factsheet by NIH, causes of Alzheimer’s likely include a combination of genetic, environmental, and lifestyle factors. The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic Alzheimer’s disease, and is present in more than 50% of patients with Alzheimer’s Disease.

A study was conducted by The Stanford University Medical Centre on 2588 people who had mild cognitive impairment and 5496 healthy elderly to find out which of the study participants had a higher risk of developing Alzheimer’s. It was found that people with mild cognitive defects who carried the risk variant of the ApoE4 gene were associated with an increased risk for developing Alzheimer’s when compared to people without the variant.  

What variants of ApoE contribute to risk of Alzheimer’s disease?

APoE2, E3, E4 are three types of alleles for APoE gene. We all carry two copies of the ApoE gene: E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4.

APOE Allele



Risk of Alzheimer’s


ε2/ε2 TT TT lower than normal E2 – Relatively rare

E3 – Most common

E4 – Lower frequency but confers higher risk

ε2/ε3 TT CT lower than normal
ε2/ε4 CT CT slightly higher than normal
ε3/ε3 TT CC normal
ε3/ε4 CT CC higher than normal
ε4/ε4 CC CC highest risk


Risk of any disease is compounded if an individual has multiple risk factors associated with a disease. So if you have family history of Alzheimer’s and are a E3/E4 or E4/E4 genotype, then your risk is further increased. Additionally, women who are carriers of E4 allele are at a higher risk compared to men. So, do not take genetic risk factors in isolation when disease risk is computed.

Prevention of Alzheimer’s

According to Alzheimer’s Association, regular physical exercise and a mediterranean diet rich in whole grains, fish, poultry, beans, seeds, nuts, and vegetable oils may lower the risk of Alzheimer’s. Other conditions like high blood pressure, high cholesterol and diabetes have shown to increase the risk of Alzheimer’s. Severe head injury that involves losing consciousness has also been linked to Alzheimer’s.


SNPedia on APOE:


Xcode is a pioneer in personal genomics, focussed on enabling personalized preventive healthcare. We are dedicated to empowering physicians, wellness professionals and customers with the most validated, accurate and actionable genomic information to positively impact and improve their client’s health and quality of life.

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