Risk Factors of Alzheimer's Disease

By ⁠Dr. Brandon Colby MD, a Personalized Preventive Medicine specialist and expert in clinical genomics.

We’ve all heard about Alzheimer’s disease and other causes of dementia. Most of us know that this disease causes progressive cognitive decline, memory loss, and cognitive symptoms.

As humans live longer and life expectancy increases around the world, so does the incidence of Alzheimer’s disease. This makes perfect sense since Alzheimer’s and other types of dementia typically occur after the age of 65 years old.

Alzheimer’s disease, along with other neurodegenerative diseases, constitutes one of the leading causes of cognitive disability in the modern world. This condition places a heavy burden on patients, their loved ones, their caregivers, and the healthcare system alike. 

But now, let’s focus on some good news. Fortunately, years of clinical trials and studies have allowed researchers to identify factors that can increase the risk of dementia and Alzheimer’s disease.

Let’s discuss the risk factors of Alzheimer’s disease, and how to prevent Alzheimer’s disease.

What Causes Alzheimer’s Disease

One of the main mechanisms that lead to Alzheimer’s disease is the accumulation of a substance called beta-amyloid or amyloid beta in our brains. This peptide collects in the extracellular space between our brain cells and forms amyloid plaques, impeding normal brain function.

Other substances, called tau proteins, accumulate in the intracellular space. Abnormalities in the metabolism of tau proteins lead to the formation of neurofibrillary tangles.¹

Healthy seniors can also develop some plaques and tangles as part of the normal aging process; however, the plaques and tangles observed in these cases aren’t as severe as the ones found in patients with Alzheimer’s.

Over time, Alzheimer’s disease leads to a significant loss of neurons and synapses. Studies have even found that certain areas of the brain shrink as the disease progresses.

But why do some people get Alzheimer’s disease, while others do not?

Is Alzheimer’s Genetic or Environmental?

Alzheimer’s disease is a multifactorial disease — as their name suggests, these diseases occur as a consequence of different genetic and environmental factors.² Some of the most common multifactorial diseases include:

• High blood pressure
• Type II diabetes
• Obesity
• Alzheimer’s disease
• Heart disease
• Asthma
• Certain types of cancer

Environmental Risk Factors for Alzheimer’s Disease

Environmental risk factors include situations and substances that you may be exposed to throughout your life; they also include lifestyle factors, which are habits and choices that lead to a greater risk of developing a disease.

Cardiovascular disease

Your heart health can impact your risk of Alzheimer’s disease. Studies have shown that people who suffer from heart and vascular diseases — such as hypertension or coronary heart disease — have an increased risk of Alzheimer’s disease and vascular dementia.³

Preventive lifestyle choices that lower the risk of heart disease include:

• Maintaining a healthy weight and avoiding obesity.
• Exercising regularly and performing aerobic physical activities.
• Managing exacerbating conditions, such as high cholesterol or triglycerides.
• Eating a heart- and brain-healthy diet, such as the Mediterranean diet or the MIND diet.
• Taking omega-3 fish oil supplements.

Traumatic brain injury (TBI)

Traumatic brain injuries — such as the ones sustained after head injuries, concussions, and accidents — increase the risk of Alzheimer’s. Studies have found that repetitive or more severe TBIs lead to an even greater increase in the risk of Alzheimer’s.

In fact, neurology studies have shown that players from the National Football League (NFL) that suffered TBIs during their careers have increased biomarkers for deposits of amyloid-beta and tau protein in their brains.⁴

To offset this risk, wear a helmet during potentially risky activities, such as contact sports, boxing, or biking. It’s also important to always wear a seatbelt and to avoid texting and driving, or driving under the influence of any substance.

Mild cognitive impairment (MCI)

MCI is defined as an intermediate stage between normal cognition and dementia. It occurs when someone experiences cognitive decline that is greater than what could normally be expected according to their age, and it’s considered to be a risk factor for dementia and Alzheimer’s disease.⁵

To reduce this risk, you can adopt preventive strategies such as increasing your cognitive reserve, playing brain games and mind exercises (such as puzzles or crosswords) regularly, and engaging in a fulfilling social life.

Substance use

Smoking tobacco and drinking alcohol excessively can significantly increase your risk of developing Alzheimer’s disease. Substance abuse can also increase your risk of other conditions, such as heart disease, that can exacerbate your risk of Alzheimer’s even more.

Genetic Risk Factors for Alzheimer’s Disease

People with a family history of Alzheimer’s disease have been found to have an increased risk of developing the disease, but why?

The APOE gene

The APOE gene is responsible for coding a protein called apolipoprotein E, which helps clear the build up of amyloid beta in our brains.⁶ There are different variants for this gene, and each variant is able to perform this task with a different degree of effectiveness, thus affecting our risk of Alzheimer’s disease.

The variants of the APOE gene are:

• APOE2: this most uncommon variant of this gene, it increases the production of apolipoprotein E.
• APOE3: this variant can be neutral; but in combination with other genetic variants, it can also increase our risk of the disease.
• APOE4: this allele leads to a decreased production of apolipoprotein E.

The APOE gene isn’t the only known risk factor for Alzheimer’s. Other risk genes for Alzheimer’s disease include genes such as ABCA7, GAB2, PICALM, SORL1, and TOMM40, among others.

Is Alzheimer’s Inherited from Mother or Father?

The genes that increase the risk of developing Alzheimer’s disease aren’t linked to our gender chromosomes (XX for women and XY for men), and you could inherit them from either one of your parents.

You inherit a copy of the APOE gene from each of your parents — a single copy of APOE4 is enough to increase your risk of Alzheimer’s, and inheriting two copies will further increase this risk.

Is Alzheimer’s Dominant or Recessive?

The genes associated with Alzheimer’s aren’t deterministic genes, which means that they don’t fully determine whether you’ll develop the disease.⁷ As a result, Alzheimer’s is neither dominant nor recessive, since ⁠it isn’t a genetic condition.

Risk genes simply increase your risk of having a disease, depending on which alleles you inherit from your parents. Additionally, your risk increases as you age — however, you can take measures to offset these risks.

The exception… Early-Onset Familial Alzheimer’s Disease

Although late-onset Alzheimer’s disease and regular early-onset Alzheimer’s disease are decided by many different factors, there is another type of Alzheimer’s disease that is more connected to your genetic data: early-onset familial Alzheimer’s disease (EOFAD).⁸ Patients EOFAD can show symptoms of Alzheimer’s during their midlife or even earlier than that, in their 30s or 40s.

EOFAD is an autosomal dominant genetic disease, meaning that inheriting a copy of the faulty gene from just one of your parents will cause the disease, and having family members with the disease is a strong risk indicator. The genes that are associated with this form of the disease are:

• Amyloid precursor protein (APP)
• Presenilin 1 (PS1)
• Presenilin 2 (PS2)

Will You Get Alzheimer’s If You Have the Gene?

The answer is: it depends. There are many different factors that come into play in the development of Alzheimer’s disease and other types of dementia, and taking preventive measures as early as possible can help greatly reduce your risk for this disease.

⁠Genetic testing for Alzheimer’s allows you to determine exactly what your genetic risk of Alzheimer’s is, so that you can take the necessary steps to protect yourself against this disease.

Can You Prevent Genetic Alzheimer’s?

As stated above, while you can’t eliminate your genetic risk of Alzheimer’s disease, there are many things you can do to offset it and reduce your likelihood of developing this condition. 

Not everyone who has genetic risk factors ends up developing Alzheimer’s disease; and on the other hand, people who don’t have a genetic predisposition to this disease do.⁹ The preventive measures that we take throughout our lives are the best tool we currently have to ward off the development of Alzheimer’s disease.

People who inherit genes for EOFAD do, unfortunately, develop this early and aggressive form of the disease. However, it’s important to keep in mind that EOFAD is extremely rare. In fact, less than 1 percent of all cases of Alzheimer’s disease are caused by EOFAD. This form of the disease has a more aggressive presentation and a strong link to family history, affecting a few hundred families around the world.

Even in cases where it’s not possible to ⁠avoid the development of Alzheimer’s disease, preventive measures can increase the likelihood of a later onset, and a slower progression with milder symptoms.

Alzheimer’s Gene Test

Thanks to genetic testing, it’s now possible to determine who has an ⁠increased genetic risk of developing Alzheimer’s disease. There are different types of genetic testing; single gene testing can identify which APOE variant you have, but other types of testing can be much more comprehensive.

For example, whole genome sequencing (WGS) can be used to sequence your entire DNA. You’ll obtain information regarding every single one of your genes, including your genetic risk of Alzheimer’s. You’ll also discover your risk of ⁠other multifactorial and genetic diseases, your carrier status for rare genetic conditions, ⁠your ancestry and ethnicity,

At ⁠Sequencing.com, we offer two different but comprehensive DNA tests — the Ultimate DNA Test and the Ultimate Genome Sequencing at affordable prices. Through our platform, you’ll be able to access numerous DNA apps and reports.

⁠Visit our Education Center to learn more about genetic testing for Alzheimer’s disease, and much more.

About The Author

⁠Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of Sequencing.com and the author of ⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠ACMG), an Associate of the American College of Preventive Medicine (⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC).