Is Alzheimer's Disease Genetic: Could It Run In Your Family?

Alzheimer’s takes a toll on its patients. As the disease progresses, a person’s personality deteriorates, and so, too, does their judgement, their memory, and their motor skills. But a diagnosis of Alzheimer’s dementia affects much more than the individual who is diagnosed.

That’s because the disease fosters feelings of fear and loss for the family, friends, and loved ones who witness its destruction, while also causing concerns for those same individuals about their own futures with the disease. So, what should you worry about when a biological parent or sibling develops dementia? Is Alzheimer's genetic, and should you be anxious about your genetic risk?

The answer is far from straightforward. Though there are many genetic mutations that are tied to Alzheimer’s, there's also an abundance of other factors that affect the development of the disease, making it difficult to determine a person's susceptibility from their genes alone.

Specialists say that people with one or more parents or siblings with Alzheimer’s are at an increased risk of developing the disease. According to a paper published in Neurology in 2019, having one immediate relative with Alzheimer’s makes you almost 2 times more likely to develop the disease than having no immediate relatives with the disorder, and having two immediate relatives with Alzheimer’s makes you almost 4 times more likely.

When this sort of pattern of susceptibility is associated with a disease, it's possible that genetics are contributing to the disease's development. But just because degenerative dementia contains a genetic component does not necessarily mean that it is inherited from a person’s parents automatically, nor does it mean that genes are the only difference between those who develop the disease and those who do not.

Of course, it's common knowledge that the mutations in our genes affect our risk of developing diseases. But those mutations affect our risk of developing diseases in distinct ways. While mutations in some genes afflict us with ailments, mutations in others merely change our chances of affliction. And while some mutations are acquired after birth, others are already inherited — and ingrained in our genetic makeup — by the time we are born.

With that in mind, genetic diseases are those that are affected by one or more genetic mutations, whether those mutations are acquired or inherited, while hereditary diseases are those that are affected by one or more inherited mutations. And though the two terms are similar, it is actually possible for a condition to be genetic without being hereditary. So, what specifically is Alzheimer's?

Studies show that there are many genetic mutations that are associated with Alzheimer's. In fact, a paper published in Nature Genetics in 2022 identifies over 70 regions of the genome that impact a person's risk of the disease, indicating that the disorder is at least partially genetic.

According to the paper, Alzheimer's has a huge "genetic component," and its "heritability is high," since a portion of the variation in its relative risk throughout the population is attributable to genes. And since many of these genes are inherited — having been passed to a person from their parents — specialists say that the disease is at least partially hereditary, too.

Read More: What You Need to Know About the 6 Stages of Alzheimer’s Disease

In the minority of instances where genes play a part in Alzheimer's, a person inherits a single mutation in a single gene that causes the development of the disease. These mutations are called "deterministic genes," and they practically guarantee that a person will acquire the dementia.

But in the vast majority of instances in which genes influence Alzheimer's, a person inherits multiple mutations in multiple genes that come together to increase or decrease their chances of developing the disease. These mutations are called "risk genes," and though they alter a person's chances of acquiring the dementia, they do not guarantee that a person will experience the disorder's deteriorative effects.

Of the many mutations that affect Alzheimer’s, those that appear in a person’s APP, PSEN1, or PSEN2 genes are the three main mutations that set off the development of the disease. These rare deterministic mutations create clumps of abnormal proteins that accumulate throughout the brain, disrupting brain cell communication and causing the development of the disease directly.

Mutations in these genes account for approximately 1 percent of all Alzheimer's cases and approximately 10 percent of all rare "early-onset" Alzheimer's cases, which occur when a person develops symptoms of the disease prior to the age of 65, typically in their 40s and 50s.

Alternatively, there are many genes that increase or decrease a person's relative risk of Alzheimer's when they are altered, with one of the main mutations affecting the APOE gene. Two copies of this gene are passed to every person by their biological parents, with one copy being passed by each parent. Coming in three common varieties, including APOE ε2, APOE ε3, and APOE ε4, each copy is associated with its own risk of Alzheimer's.

Having the APOE ε2 genes decreases a person’s risk, and having the APOE ε3 gene neither decreases nor increases a person’s risk. But the APOE ε4 gene predisposes a person to developing the disease, particularly later in life. Around 40 to 65 percent of all people with Alzheimer's have at least one copy of the APOE ε4 gene, which is closely associated with the common "late-onset" form of the disease.

Read More: Is Alzheimer's Disease Fatal, and How Does It Lead to Death?

Around 15 to 25 percent of people carry a copy of the APOE ε4 gene, and as many as 5 percent of people carry two copies, placing them at a greater risk of Alzheimer's than if they carried only one. But whether they possess one copy or two, individuals with the APOE ε4 gene aren't always destined for cognitive decline.

In fact, there are all sorts of people who never see symptoms of the disease, despite a predisposition to the disorder idling inside their genes. And there are a smattering of other factors that impart similar, if not greater, influences on whether they develop Alzheimer's. Specialists say, for instance, that aging is the greatest risk factor for the disease, far above genetics, with a person's risk doubling every five years after they reach the age of 65.

Other risk factors relate to a person's lifestyle. Studies show, for instance, that a person's mental agility impacts their susceptibility to dementia, suggesting that socialization and similarly stimulating activities can reduce Alzheimer's risk. Sleep, diet, exercise, and exposure to toxins and pollutants also play a part in determining a person's predisposition, meaning that one of the best ways to act against dementia is not by fretting about genes, but by developing healthy habits.

Read More: The 4 Main Types of Dementia