The strongest genetic risk factor for late-onset Alzheimer’s disease is the E4 variant of Apolipoprotein E (ApoE), meaning that two of the amino acid building blocks of the protein are different. However, though 14% of the world’s population carry this variant (AlzGene), many will not develop the disease. People with one copy of E4 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 E4 variant is less capable than other types of ApoE to repair neurons and serve other functions important for brain health. Alternatively, the E4 variant may have toxic effects on the brain.
Since ApoE e4 is a primary risk factor for Alzheimer’s disease, drugs that target ApoE may prevent the disease. The Alzheimer’s Drug Discovery Foundation (ADDF) funds drug discovery to accelerate the development of novel therapeutics specifically targeting ApoE pathological mechanisms. 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 by filtering with the ApoE program
The ApoE E4 variant may determine the effectiveness of a given prevention strategy. Two recent examples you may remember from our coverage:
• Scientists observed that physical activity was associated with less brain atrophy in E4 carriers but not non-carriers .
• The omega-3 fatty acid DHA appears to offer little protection from dementia for E4 carriers though it may protect non-carriers.
The E4 variant may also determine if anti-hypertensive ACE inhibitor drugs , education, and non-steroidal anti-inflammatory drugs like 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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