Apo-E testing and impact on one’s risk for developing dementia has been getting more attention over recent years.
Advances in testing abilities, increased interest in knowing one’s own life risks and having a better sense of control over our futures has driven some of this increased attention. Famous celebrities, such as Chris Hemsworth (aka Thor), have also come forward to share their own genetic testing results and how it has impacted their lives.
Many people such as Hemsworth are using results of tests like this to take their own risk more seriously and work to reduce it with active measures which we explore in depth here at Deter Dementia.
Alzheimer’s Disease is by far the most common type of dementia with estimates ranging from 60-80% of all dementias being caused by this disease. Rates of developing Alzheimer’s increase with age and as our populations live longer, the risks of developing this disease increase as well.
The genetics of Alzheimer’s Disease are complex, particularly when it comes to Apo-E. The subtype of Apo-E that increases Alzheimer’s risk (Apo-E4) is quite common with estimates of over 25% of the North American population carrying one copy of the Apo-E4 allele.
Evidence is clear that not everyone with an Apo-E4 allele will develop Alzheimer’s. However we do know that the presence of this allele appears to increase risk.
Apolipoprotein-E (Apo-E) helps with the body metabolizing and moving cholesterol and fats around in our bodies. There are 3 versions of the Apo-E gene (E2, E3, and E4) – let’s take a dive deeper:
Apo-E2 – less than 10% of the world’s population has this version and interesting it appears to be PROTECTIVE against Alzheimer’s. It is also correlated with lower cholesterol and lower rates of heart disease. There can be rare negative cardiac effects of having Apo-E2 as well.
Apo-E3 – this is the most common version of the allele and is present in over 75% of the population. We use this as a baseline to estimate risk of developing Alzheimer’s given its prevalence and it correlates with fairly normal levels of blood cholesterol.
Apo-E4 is the variant that is most concerning for people. It is present in about 15% of people around the world and is associated with a significantly higher risk of getting Alzheimer’s. If one has a single copy of this allele, their risk of developing Alzheimer’s is 3x higher than the general population. If they have two copies, the risk goes up 12x!
There are other negative aspects to Apo-E4 as well including increased risk of cardiovascular disease, increased risk of cerebral amyloid angiopathy (can cause bleeding in one’s brain), and more.
So does this mean if you have two alleles of Apo-E4 you are guaranteed to get Alzheimer’s disease?
No. The presence of this gene does increase risk but does not guarantee anyone develops the disease. Understanding one’s risk can be helpful as it may inform how you live your life and how strongly you focus on preventive strategies and approaches.
The opposite is true as well, individuals who do not have any Apo-E4 alleles can still develop Alzheimer’s as well – they just aren’t as likely to do so as those with the Apo-E4 alleles.
Why does Apo-E4 increase risk?
Risk appears to increase because the presence of Apo-E4 makes it more difficult for our brains to clear out certain proteins from our brain (amyloid-beta) which can disrupt brain function and directly appear to increase risk of developing Alzheimer’s. There is also increased inflammation in the brain in those with Apo-E4 which can further increase one’s risk of developing Alzheimer’s.
So what’s the good news?
The good news is that we can do something to change how our genetic makeup affects our likelihood of getting certain diseases. Lifestyle factors (diet in particular) can play a big role in reducing the negative effects that Apo-E4 has on our brains (and the rest of our body). If we reduce our saturated fat intake and increase our omega-3 fatty acid intake, it appears to improve our body’s ability to handle and process unhealthy fats.
We thus have some control in reducing our risk overall despite a potential “bad hand” we’ve been dealt genetically if we do have the Apo-E4 alleles.
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