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Do Genetic Factors for Alzheimer’s Disease Increase COVID-19 Risk?

People with a genetic variation that increases the risk of developing Alzheimer’s disease are also more susceptible to get COVID-19, claims one study published by the Journals of Gerontology: Series A. However, there is no cause for alarm yet, as the study is quite small and not all experts agree there’s a direct link between having Alzheimer’s and developing a severe case of COVID-19.

What Is the Link Between Alzheimer’s and COVID-19?

According to this study, people who have two copies of a variant of the ApoE gene, called the ApoE4, are twice as likely to develop a severe case of COVID-19 as people who carry the ApoE3 variant of the same gene. The presence of two copies of the ApoE4 is one of the known genetic risks for dementia.

The researchers came to this conclusion after analyzing the data for the patients diagnosed with COVID-19 in England and Wales between March and April 2020.

In a group of 622 people hospitalized with coronavirus, genetic testing revealed that 37 patients had two copies of the ApoE4 gene. While the number might not seem high, the problem is the ApoE4 is rather rare.

A major analysis of the information provided by Biobank UK, a research center that has collected genetic data from 500,000 volunteers aged 48 to 86, revealed that only 9,000 people had two sets of ApoE4, while more than 223,000 had two copies of the ApoE3 gene.

Since the chances of having the ApoE4 variant are rather low, the number of carriers infected with coronavirus appears more significant.

According to the British researchers, comparing the numbers and applying a statistical model, this means that out of 100,000 people with two sets of ApoE4, 410 would test positive. For the ApoE3 group, only 179 out of 100,000 people would test positive.

The Controversy

One of the main issues with this study is that it looked at hospitalized patients with COVID-19 and, as everybody knows by now, those who ended up in hospitals were elderly people.

In England and Wales where the study took place, dementia was one of the most common underlying conditions of those who died of COVID-19. Many pointed out that since you’re looking at elderly patients, you’re bound to find more people with dementia among them.

“It is not just age: this is an example of a specific gene variant causing vulnerability in some people,” said David Melzer, a professor of epidemiology and public health at Exeter University and a co-author of the study, quoted by \”The Guardian\”.

 However, other experts find this study inconclusive.

“An important limitation of the current paper is that this type of observational study cannot prove that the APOE4 gene is the cause of the observed increased risk of COVID-19. The scientists did a thorough job of trying to control for other things associated with APOE4 that could account for the risk, but it is still possible that there is an unknown related factor causing the increased risk,” says professor Tara Spires-Jones, UK Dementia Research Institute Group Leader at the University of Edinburgh.

What Is ApoE4?

ApoE stands for apolipoprotein E, which transports fats and supports injury repair in the brain tissue. The variant known as ApoE4 has been linked with an increased risk of developing dementia. People who have two copies of the ApoE4 are 14 times more likely to develop AD than people who have the ApoE3 variant. At the same time, people with another variant called ApoE2 have a low risk of developing dementia.

Apolipoprotein E may be involved in brain plaque formation. Plaque deposits—in the form of amyloid-beta (Aβ) peptide—are a hallmark of Alzheimer’s.

Amyloid-beta is a compound that accumulates in the brain and ends up disrupting communication between brain cells, damaging, and eventually killing them. The theory is that ApoE4 is involved in the formation of amyloid-beta deposits, by direct protein-to-protein interaction, although the exact mechanism is not yet fully understood.

What Are the Risks of Getting Two Copies of the ApoE4?

Apolipoprotein E has three variants: 2, 3, and 4. A person inherits one such gene from the mother and one from the father so you can get any combination of those variants.

Studies have shown that the ApoE3 variant is more prevalent. Up to 60% of the population has two copies of ApoE3, and these people are considered as having an average risk of developing Alzheimer’s. Health statistics suggest that roughly 25% of this group will develop AD in their 80s.

About a quarter of the population has just one copy of ApoE4, which increases the risk of AD by more than two times.

Only a small percentage of the population, 2%, will inherit a double set of ApoE4, which increases the risk of AD three to five times. This does not mean they will absolutely develop dementia.

Other Genetic Factors That Increase the Risk of Alzheimer’s

A lot of research has been conducted on the genetic risks for AD, but there’s a lot more to be done until scientists will be able to explain the mechanisms that trigger this condition.

The discovery of the link between ApoE4 and dementia is considered a breakthrough, but experts say there might be other genetic factors that put some people at risk for AD that have not yet been discovered. Lately, there have been other studies focusing on other gene variants that might play a role in the development of this disease.

Other genes linked to an increased risk of Alzheimer’s include CLU, CR1, MS4A, BIN1, PICALM, CD33, ABCA7, CD2AP, and EPHA1. These play a role in the immune system, inflammation, fat metabolism, or transport within cells.

How Great Is the Risk of Developing Dementia If You Have AD in the Family?

When you have a parent or sibling diagnosed with Alzheimer’s disease, it’s only natural to wonder if you might develop dementia at some point in your life. When doctors talk about genetic factors, they refer to two different types of genes—risk genes and deterministic genes.

 The ApoE4 linked to AD is a risk gene, which means that people who carry two copies of this variant are at risk of developing dementia, but this is not a certainty. There are probably other factors than genetics involved of which we don’t know much at this time.

Deterministic genes are those that guarantee that people who carry them will get a certain disease. There are such genes for Alzheimer’s, but fortunately, they are extremely rare. These genes have been found in only a few hundred extended families around the world and account for less than 1% percent of AD cases. Familial Alzheimer’s causes early onset of the disease, usually affecting people in their 40s and 50s, whereas AD usually appears in people over 65.

Is There Any Reason to Worry?

The British study linking Alzheimer\’s to COVID-19 got a lot of attention as scientists all over the world are trying to understand the new coronavirus.

However, the findings are not exactly significant at this time, so you shouldn’t probably worry your loved one struggling with Alzheimer’s will develop a severe case of COVID-19. Chances are he or she is no more at risk than other elderly people without dementia.

One possible risk concerns people in the early stages of AD who might have trouble understanding the coronavirus pandemic and following the recommended preventive measures, such as wearing a mask or washing their hands more frequently.

Making sure they stay safe at this time is the best way to protect them against COVID-19.

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