Dr. Betty Lacy, M.D.

The Alzheimer's Gene: APOE4 thumbnail image


What is the APOE gene?

The APOE gene is a cholesterol-carrying gene. Everyone inherits a copy of the APOE gene. You inherit one copy from your mother and one from your father. There are 3 variations of APOE: Type 2, Type 3, or Type 4. These are called alleles. The APOE4 gene is involved in 1700 interactions in your body, so it is pretty important. There are 6 possible combinations of alleles:

  • APOE 2/3
  • APOE 2/2
  • APOE 2/4
  • APOE 3/3
  • APOE 3/4
  • APOE 4/4

The APOE 4 gene carries significant health risks. It is known to increase the risk of Alzheimer’s disease and cardiovascular disease because of the various reactions in the body (see APOE Interactions below). It is called the Alzheimer’s gene but it contributes to many diseases including cardiovascular disease and stroke.

What is my specific risk for Alzheimer’s Disease?

Alzheimer’s disease is caused by many factors. There are approximately 30 known genes that contribute to Alzheimer’s disease but APOE4 has the greatest risk. If you have one copy of the APOE4, you have a 2-3 times greater risk of acquiring AD than the general population. If you have 2 copies APOE4/4 you have a 10-13x greater risk than the general population. Keep in mind this is for Late-Onset Alzheimer’s Disease and not related to Early Onset Alzheimer’s Disease. Just because you have the APOE4 does not mean that you will get the disease. There are no guarantees you will get AD or not get it. Body-Brain Health is focused on optimizing your health to reduce your risk of AD.

How does the APOE4 gene affect my body?

So far we know that the APOE4 increases inflammation increases amyloid beta in the brain, decreases glucose utilization in the brain, reduces mitochondrial function (cellular energy), reduces cholesterol/lipid metabolism, reduces nerve growth factor and cellular communication (synaptic function). APOE4 makes cells more susceptible to toxins and oxidative stress.

If I have the APOE4, what can I do to reduce my risk?

It is important that you participate in a Brain Health Program and obtain an annual Cognoscopy (evaluation of your cognitive health). Make health a priority! Remember even little changes can make a difference. Having the APOE 4 may favorably better your chances of lifestyle changes having big impact on improving your health. You can begin applying these changes outlined by the SLEDS acronym.

  • S= Sleep 7-8 hours
  • L= Make lifelong learning a priority
  • E= Exercise daily
  • D= Optimize your diet and weight
  • S= Reduce Stress and Socialize regularly

Why would I want to get tested for this gene if it tells me I may get Alzheimer’s disease?

The APOE4 means you are at risk for Alzheimer’s Disease, but it is not a slam dunk that you will get it. We know the changes in the brain begin 10-20 years before one develops memory impairment. Testing for the APOE 4 gene gives you an opportunity to understand your genetic risk for Alzheimer’s disease and other diseases. Remember the APOE 4 gene also puts you at risk for cardiovascular disease and stroke because of its involvement in cholesterol metabolism. If you are positive for the APOE 4, you can begin to take steps to reduce its risk by following more closely your cholesterol, glucose and inflammatory markers. Knowledge of dietary and lifestyle factors will also be important to reduce the risk of cardiovascular diseases(CVD)and neurodegenerative disorders. Knowing what your risk is and what you can do about it, gives you a head start on monitoring and making changes that impact your health and reducing your risk of dementia.

How do I get tested for the APOE4?

Doctors and clinics specializing in Brain and Cognitive Health, 23andme.com, ancestory.com all provide testing. It can involve a simple blood or saliva test.

Why should I even care about my genes, I just want to live life on life’s terms?

There is not a right or perfect way to live, but knowledge does bring power and knowing your genetic risk of certain diseases can guide you in everyday choices to improve you and your family's lives. Based on our scientific understanding of disease processes, knowing your genetic predisposition to various diseases lets you in on the body’s hidden secret that has only recently been unlocked: GENES. The Genome Wide Association Studies (GWAS) is a study that continues to offer us information on various diseases, so we can understand their genetic underpinnings. These diseases were once thought to be a role of the dice and unavoidable. A glimpse into our human DNA and genetic variations allows us a unique opportunity never before possible. With this information, we can lead better healthier lives and prevent these diseases. https://www.genome.gov. Genetic testing and counseling will soon be available in most clinics and doctors offices.

What are specific INTERACTIONS in the body caused by the APOE4 gene?

  • Synaptic function lowered
  • Glucose metabolism lowered
  • Neurogenesis – lowered
  • Alpha B clearance – lowered
  • Vascular function – lowered
  • Mitochondrial function – lowered
  • Lipid/cholesterol metabolism – lower
  • Aberrant brain activity – heightened
  • Tangle formation – heightened
  • Alpha Beta aggregation – heightened
  • Neuronal toxicity – heightened
  • Brain atrophy - heightened
  • Potential Loss of Function and gain of Toxic function

Related Links and Resources

1) More on genetic testing: https://www.apoe4.info/wp/thinking-about-testing/. This is a great site for those with questions about whether or not to get tested, along with a test to guide you in the process

Links > What If You Knew it was Coming For You?

Links > The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline

Links > APOE 4: Dr. Betty's Family Story

Betty Lacy, M.D.

Dr. Lacy specializes in the field of brain health, cognitive resiliency, genetics, and mental health. Learn More >

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