The APOE gene and it’s influence on Alzheimer’s disease

In April 2017, the Food and Drug Administration (FDA) approved 23andme Alzheimer’s genetic test to evaluate the 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 E (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 a 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.  

 

Which ancestry genetic testing company is the best for testing APOE variants?

CHIP Version ACTN3 SNPs
23andMe (Use your 23andme raw data to know your APOE Variant)
v1 23andme Present
v2 23andme Present
v3 23andme Present
v4 23andme Present
V5 23andme (current chip) Present
AncestryDNA  (Use your ancestry DNA raw data to know your APOE Variant)
v1 ancestry DNA Present
V2 ancestry DNA (current chip) Present
Family Tree DNA  (Use your FTDNA raw data to know your APOE Variant)
OmniExpress microarray chip Present

23andme Alzheimer’s test: Which variants of ApoE contribute to the risk of Alzheimer’s disease?

23andme Alzheimer’s test collectively constitutes the analysis of APOE e2, 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

rs429358

rs7412

Risk of Alzheimer’s

Distribution

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. Concussions has also been linked to Alzheimer’s.

References:

SNPedia on APOE: http://www.snpedia.com/index.php/APOE

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