The APOE Haplotype and Its Relationship with Alzheimer’s: Can Risk Be Modulated?

Alzheimer's is one of the most prevalent neurodegenerative diseases in the world, and genetics plays a crucial role in its development. Among the most studied genetic risk factors is the APOE haplotype (Apolipoprotein E), a key protein in lipid metabolism and the maintenance of neuronal function. In this article, we will explore the relationship between the APOE haplotype and the risk of Alzheimer's, as well as strategies that could help mitigate this risk.

What is the APOE haplotype?

The APOE gene, located on chromosome 19, encodes the apolipoprotein E protein, which is involved in the transport and metabolism of cholesterol in the central nervous system. There are three main variants of this gene (alleles):

• APOE-ε2: Considered protective against Alzheimer's.

• APOE-ε3: Neutral variant, the most common in the population.

• APOE-ε4: Associated with a higher risk of developing Alzheimer's.

Individuals inherit two copies of the gene, one from each parent, resulting in different genetic combinations. The presence of one copy of APOE-ε4 increases the risk of Alzheimer's compared to APOE-ε3, while having two copies of APOE-ε4 significantly multiplies the risk.

How does the APOE haplotype influence the risk of Alzheimer's?

Studies have shown that individuals with the APOE-ε4 allele have up to a three times greater risk of developing Alzheimer's if they have one copy and up to 10 times greater if they have two copies, compared to those with the APOE-ε3/ε3 genotype. This increased risk is due to several mechanisms:

1. Decreased clearance of beta-amyloid: APOE-ε4 hinders the removal of beta-amyloid plaques in the brain, contributing to neurodegeneration.

2. Increased neuronal inflammation: This allele has been observed to promote an inflammatory environment that worsens brain damage.

3. Alterations in lipid metabolism: APOE-ε4 is associated with a decreased ability to repair neurons and maintain synaptic integrity.

Can the risk of Alzheimer's be modulated in APOE-ε4 carriers?

Although genetic predisposition cannot be modified, there are preventive strategies that can help reduce the risk of developing Alzheimer's, even in individuals with the APOE-ε4 allele:

1. Diet and nutrition

• Following a diet rich in fruits, vegetables, fish, olive oil, and nuts has been shown to reduce the risk of cognitive decline.

• Limiting the consumption of saturated fats and refined sugars is important, as they affect neuronal function and increase inflammation.

• Ensuring adequate intake of omega-3 (DHA and EPA), found in fatty fish like salmon, can improve brain health.

• Maintaining healthy blood pressure, optimal cholesterol levels, and a proper body weight is key to preventing Alzheimer's.

• Type 2 diabetes is closely related to the risk of dementia, and strong interpersonal relationships also protect against cognitive decline.

2. Regular physical exercise

• Aerobic activity such as walking, running, or swimming improves cerebral circulation and promotes neuroplasticity. It has been shown that 30 minutes of moderate physical activity daily reduces the risk associated with the APOE-ε4 allele.

• Resistance training and coordination exercises have also shown protective effects on the brain.

3. Cognitive stimulation

• Keeping the brain active with reading, learning new languages, or creative activities can strengthen cognitive reserve.

• Participating in strategy games, puzzles, or social activities reduces the risk of mental decline.

Conclusion

The APOE haplotype, especially the APOE-ε4 variant, is a genetic factor that influences the risk of developing Alzheimer's. The combination of a healthy diet, regular exercise, mental stimulation, control of metabolic diseases, adequate sleep, and stress management can help modulate this risk and promote a healthy cognitive life. Although genetics plays an important role, lifestyle remains a key factor in Alzheimer's prevention. With N-GENE, you can understand your patients' risk and assist them with a preventive strategy. Request a demo and start using the tool in consultation today.