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The Genetics of Alzheimer’s Disease

John Bankston John Bankston April 22, 2021
Medically reviewed by Susan Kerrigan, MD and Marianne Madsen

Few diseases inspire as much fear as Alzheimer’s disease. Cancer, heart disease, kidney failure–they all destroy the body. Alzheimer’s disease destroys the mind. Sufferers are robbed of their memories and eventually their ability to care for themselves. It’s a slow, progressive, debilitating disease with few treatment options and no cure. In a weird way, it’s a sad side effect of increasing longevity–the older we get, the greater our chances of developing Alzheimer’s disease. Yet a growing body of research has mapped it on a genetic level––including the recent discovery of two genes associated with an increased risk. What does this mean for future treatments or even cures? Most importantly, what can we do to reduce our own risks today?

 

All About Alzheimer’s Disease

 

Defined as “a neurodegenerative disorder that involves worsening dementia and the formation of protein plaques and tangles in the brain,” Alzheimer’s disease directly affects the hippocampus. Because this is where memories are formed and stored, memory loss is often an early indicator. Using medical imaging, like MRIs, doctors can see the damage wrought by Alzheimer’s disease because the loss of vital brain nerve cells called neurons actually causes the hippocampus to shrink.

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Dementia - Overview

Dementia - Overview

Recently, researchers compared the brains of healthy subjects to those with Alzheimer’s disease. They were able to identify two dozen markers associated with the disease. Many were already known. For example, the risk gene apolipoprotein E (APOE) is connected to the most common form of the disease, late-onset Alzheimer’s disease, which usually starts in adults over the age of 65. There are three forms of this gene, but the least common, APOE e2, actually seems to reduce one’s risk for developing Alzheimer’s disease. The most common form, APOE e3, doesn’t seem to affect risk at all. The APOE e4 gene’s rate of occurrence falls between the other two. This is the one doctors are on the lookout for since it increases the risk of developing the disease. Like many things from height to hair color, your risk for Alzheimer’s disease is inherited. If both your parents have the APOE e4 gene, you have a greater chance of developing the disease than if only your mother or your father has it. 

 

Other genes that have been connected to late-onset Alzheimer’s disease include one that regulates how your body uses cholesterol, ABCA7, and PICALM, which is connected to the way our neurons communicate. One gene linked to the disease, CR1, produces protein––when it is deficient, there is a greater chance that the brain will become inflamed. The recent study similarly examined genes that increased the risk for Alzheimer’s disease by looking at how they affected the brain’s protein production. They also looked at genes that contribute to plaque formation and cell death. The discovery by the researchers of two new genes, PTPN9 and PCDHA4, help scientists and doctors who treat Alzheimer’s disease better understand how it is expressed genetically and what happens to the brain when certain genes are present.

 

Yet despite knowing the genes that increase risk, most doctors don’t recommend genetic testing. That’s because the presence of the gene doesn’t always mean a patient will get the disease. The exception is early-onset Alzheimer’s disease which can afflict patients in their 30s. With other genes, inheriting them from both parents doesn’t mean you will get the disease, but inheriting a mutated Amyloid precursor protein (APP), Presenilin 1 (PSEN1), or Presenilin 2 (PSEN2) from either parent makes it likely you will have the disease before your 65th birthday.  

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Dementia - Genetics

Dementia - Genetics

Reducing Risk

 

Identifying the genes that drive a disease is an important step toward treatment or a cure, but it’s just a first step. COVID-19’s genetic code was mapped over a year ago, yet treatments have been limited while a cure has yet to be discovered. What has been developed are ways to prevent the disease––vaccines. Turns out there are some ways to “inoculate” yourself from Alzheimer’s disease–and you don’t even have to get a shot. Just as a healthy diet can overcome the genetic “gifts” from overweight parents, what we eat may reduce our risk of developing the disease. 

 

Like the Dietary Approaches to Stop Hypertension (DASH) diet which helped those at risk for heart disease, the Mediterranean-DASH Intervention for Neurodegenerative Delay or MIND diet does the same with Alzheimer’s disease. By eating a diet rich in plant-based foods and low on red or processed meats, many participants in one study cut their risk of developing Alzheimer’s disease by more than half. Eating plenty of whole grains, green leafy vegetables, nuts, and berries also aided participants’ memory while slowing their cognitive decline. 

 

Adopting a healthier diet isn’t the only thing you can do to reduce your risk. Learning a new skill, from quilting to photography, strengthens connections between parts of your brain just as a reinforced bridge strengthens connections between communities. So if you think it’s too late to learn a foreign language or take a class at the local university, the truth is the right time is right now.

Doctor Profile

John Bankston

Author

John Bankston is a published author of over 150 nonfiction books for children and young adults including biographies of Jonas Salk, Gerhard Domak, and Frederick Banting.

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