APOE4 and Alzheimer's Risk - BrainMind Alzheimer's Prevention Series

Video 5: APOE4 and Alzheimer’s Disease
In collaboration with BrainMind, Dr. Isaacson introduces the gene APOE4 and its implications on Alzheimer’s Disease and brain health.

About Dr. Richard Isaacson:
Dr. Richard Isaacson is the founder and former Director of the Alzheimer’s Prevention Clinic at the Weill Cornell Memory Disorders Program. He is currently the director of Brain Health at the Atria Institute. A leading expert on Alzheimer’s Disease (AD), Dr. Isaacson is passionate about providing the latest evidence-based options for treatment and risk reduction. His research focuses on individualized clinical management of AD using emerging principles of precision medicine. He also oversees a robust AD therapeutics and education research program.

Nature vs. Nurture (What is Causing Alzheimer’s Disease?)

APOE (Apolipoprotein E: lipid, protein) gene
● Variants (or different types) of the gene exist and people have different combinations of
APOE alleles. Receive two copies of APOE gene: one from mother, one from father
APOE variants
1. APOE2: least common, reduce the risk of Alzheimer’s and also protect against
cardiovascular and cholesterol related diseases
2. APOE3: most common, don’t affect the risk of Alzheimer’s
a. 50~65% of the population has APOE3/APOE3 as their genetic combination of
alleles
3. APOE4: moderately common, increases the risk of Alzheimer’s
a. 25% of the populations have at least one copy of APOE4
b. 1% of the populations has two copies of APOE4

Although people with more copies of the APOE4 variant have a higher chance of developing. Alzheimer’s disease genetics doesn’t determine everything.

Neutralizing the effects of APOE4
● Effectively control other factors that contribute to the risk of Alzheimer’s disease
besides the APOE4 gene:
1. Genes that work in collaboration with the APOE4 gene that might increase or
decrease the risk
2. Lifestyles changes
3. Medical Conditions (i.e. Cardiovascular Conditions)
4. Medications

Precise, Personalized Medicine: Delivering individualized care based on a person’s genetics
1. Pharmacogenomic: How genes affect a person’s response to drugs?
2. Nutrigenomic: How genes affect a person’s response to nutrients?

What leads to Alzheimer’s disease besides the APOE4 gene or in combination with the
gene?
● Gender: Women with the gene are at higher risk than men
○ However, men with high cholesterol can also have a high risk
● Age: people at a younger age are more protected
○ With aging, in combination with the APOE4 gene, people can be at higher risks
● Things to consider/ current studies:
○ Will people with head trauma have a higher risk?
○ Will exposure to certain pesticides increase the risk?
○ What dosage of vitamins is optimal or necessary for those with the APOE4
variant?
● Ultimately, the genes alone do not definitively cause Alzheimer’s and prevention might
be possible.