Apolipoprotein E (ApoE) is a Protein
Apolipoprotein E (ApoE) is a protein combined with fat (lipids) in the body which is responsible for packaging cholesterol and other fats and carrying them through the bloodstream. The APOE gene codes for this lipoprotein and is important for:
- Absorbing cholesterol from the intestines.
- The uptake of triglyceride rich lipoproteins by the liver,
- Transporting cholesterol and cholesterol like molecules, such as beta amyloid, out of brain cells.
- A marker in prevention of disorders that affect the heart and blood vessels.
Through genetic testing such as 23andme, your APOE genotype not only addresses genetic factors in cholesterol management, but can predict your genetic disposition to late stage Alzheimers Disease. There are 3 different alleles (types) of the APOE: E2, E3, E4 and everyone possesses two of these alleles, creating genotype combinations of E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, and E4/E4. The APOE2 (15%) is considered protective, APOE3 is neutral (most common genotype-65%) while the APOE4 (20%)is considered “high risk” for Alzheimers.
APOE4: The Risk Factor Gene
APOE4 is called a risk-factor gene because it increases a person’s risk of developing the disease, but inheriting an E4 allele does not mean that a person will definitely develop Alzheimer’s. Some people with an APOE4 allele never get the disease, and others who develop Alzheimer’s do not have any APOE4 alleles. It’s helpful to remember that in 75% of people, genetic predisposition does not lead to a diagnosis of Alzheimers, and knowing APOE genetics can empower patients like no other time in history.
Unlike any other time in history, we have the knowledge to know and support our DNA, and radically change our medical outcomes. Below are my top 5 reasons why knowing your APOE allele (and your children’s) could help you tailor your lifestyle choices.
- Cardiovascular disease is the #1 killer of both men and women, and will show up long before Alzheimer’s does. ApoE status can decrease atherosclerosis but it’s important to know your genotype and how it is influencing your lipids. Knowledge of genetic influences can determine appropriate nutritional, supplemental, and medication interventions to prevent cardiovascular disease through proper cholesterol management.
- Each genotype has it’s own unique lifestyle profile, and knowing this allows the patient to make educated choices about their future. E4 alleles do better with low fat and lower animal proteins. E3 do better with alcohol than an E4, and E3 do better with high intensity workouts than E4. Again, like reason #1, not every body or genotype is same, so either should their treatment plans. There is emerging evidence that epigenetic mechanisms contribute to Alzheimer’s disease and whether protective, benign, or harmful, may help explain, for example, why one family member develops the disease and another does not. Scientists are learning more about Alzheimer’s-related epigenetics, with the hope of developing individualized treatments based on epigenetic markers and their function.
- Research shows that head trauma can increase incidence of Alzheimers disease, and with 25% of the population carrying at least one APOE4 allele, the two can be a poor mixture. ApoE is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS) and is critical for membrane repair and remodeling. APOE4 alleles are expressed less in the cerebral spinal fluid and brain, thus inhibiting proper repair and detoxification of the brain. (remember those beta amyloid plaques?) Knowing your genetics could positively influence the sports and activities you choose to participate in and adds more warrant to always wearing a helmet, seat belt, and to avoid high risk activities. In a recent study of college athletes, 75% of those asked agreed it would be valuable information to know there genotype. In his book Change your Brain, Change Your Life, Dr. Daniel Amen (an expert in TBI with 1000’s of SPECT scans showing the long standing damage head traumas can do) goes one step further: he is adamant against allowing children to play sports that lead to head traumas. Just say NO, because no matter if your child is unhappy about it now, they will thank you later.
- APOE4 alleles may decrease the effectiveness of DHA, an essential omega fatty acid found in fish oils. Some research is showing that omega 3’s from algae and NOT fish oils are better absorbed and utilized by the E4 genotype. One recent study found that simply eating fish once a week and eating moderate to high amounts of food source omega’s 3 demonstrated slower rate of cognitive decline in ONLY E4 carriers. With fish oil being the cure for everything these days, it might be worth knowing whether or not it will help a patient with future cognitive decline.
- APOE genotype can likely affect the response to estrogen replacement therapy. Research suggests that many of the beneficial effects estrogens on the brain are dependent on ApoE and specific APOE alleles. However, the clinical research is contradictory on how estrogen therapy may affect the long-term brain health in people with or without the E4The research is somewhat conflicting, but I would look into more natural choices for menopause, and would not encourage HRT, birth control, or estrogen like compounds in a patient without knowing their APOE genotype.
Dr. Hillary Lampers ND gained a BS in Natural Health Sciences with a Major in Nutrition and PreMed focus (2002) and a doctorate in Naturopathic Medicine (2007) both from Bastyr University. She is founder and co-owner of Sky Valley Healing Arts in Snohomish, WA.
Dr. Hillary has integrated her training and knowledge to help patients with pain elimination, disease prevention, anti-aging, and lifestyle management. She is creator of the Get It Back online health coaching program, where she works 1:1 with patients, resetting hormone and brain chemistry to look and feel better. She has 15 years of advanced training in NeuroCranial Restructuring®, a revolutionary cranial and neurological therapy, and is currently one of only 18 globally certified practitioners.
When not learning from her patients, Dr. Hillary is spending time with her husband and two daughters in their garden, in the mountains, or traveling! Learn more about Dr. Hillary and her practice at drhillarylampers.com.
 Mahley, RW. Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism. Arterioscler Thromb Vasc Biol. 2016 May
 Hercher, LS, Caudle, M, Griffin, J, Herzog, M, Matviychuk, D, Tidwell, J. Student-Athletes’ Views on APOE Genotyping for Increased Risk of Poor Recovery after a Traumatic Brain Injury. J Genet Couns. 2016 May 21.
 Change Your Brain, Change Your Life. Dr. Daniel Amen, Copyright
 Van de Rest, O, Wang, Y, Barnes, LL, Tangney, C, Bennett, DA, Morris, MC. APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline. Neurology. 2016 May 4.
 Brown CM, Choi E, Xu Q et al. (2008) The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol. Neurobiology of aging 29, 1783-1794.