Apolipoprotein E4: Not Just a Genetic Risk Factor

The strongest genetic risk factor for late-onset Alzheimer’s disease is the E4 variant of Apolipoprotein E (APOE4). Though 14 percent of the world’s population carries this variant, many will not develop the disease. People with one copy of APOE4 are three to four times more likely to develop Alzheimer’s; people with two copies are 15 times more likely to develop the disease. 

Why does APOE e4 raise the risk of Alzheimer’s disease? A variety of explanations have been proposed. It’s possible that the APOE4 variant is less capable than other types of APOE4 to repair neurons and serve other functions important for brain health. Alternatively, APOE4 may have toxic effects on the brain. 

Since APOE4 is a primary risk factor for Alzheimer’s disease, drugs that target it may prevent the disease. The Alzheimer’s Drug Discovery Foundation is funding several drug programs specifically targeting APOE4. To date, 19 projects have been funded, totaling over $4.27 million. More information about these grants can be found in the ADDF grants portfolio.

The APOE4 variant may also determine the effectiveness of a given prevention strategy because those with and without the gene variant react differently. For example,ur coverage

     •   Scientists observed that physical activity was associated with less brain atrophy in APOE4 carriers but not non-carriers.

     •   The omega-3 fatty acid DHA appears to offer little protection from dementia for APOE4 carriers though it may protect non-carriers. 

The APOE4 variant may also determine if anti-hypertensive ACE inhibitor drugs, education, and non-steroidal anti-inflammatory drugs such as ibuprofen are effective in protecting the brain from aging and dementia. The evidence for these claims is generally very limited. However, it’s clear that protecting ourselves from Alzheimer’s disease may require a better understanding of how our genes interact with our health choices.

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