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Alzheimer’s Disease: APOE4 Gene and Memory Loss

Did you know that people with the APOE4 gene are at higher risk for memory loss and brain diseases, such as Alzheimer’s?

Alzheimer's risk is partly influenced by genetics, though it’s not the only factor, as age, heart problems, diabetes, obesity, smoking and loneliness, among others, are other factors that come into play.

The discovery of the link between the APOE4 gene and Alzheimer’s has led to new research being made into how we can target this gene to reduce the risk of getting Alzheimer’s and improving our health span.

Let’s go over what we know about APOE4!

How APOE4 Affects Our Health

The APOE4 allele of the apolipoprotein E (APOE) gene affects many areas of our bodies. These include:

• Blood-brain barrier: APOE4 can damage the blood-brain barrier, which can lead to cognitive decline.
• Alzheimer's disease: APOE4 is the primary genetic risk factor for sporadic Alzheimer's disease.
• Mitochondrial dysfunction: APOE4 can cause mitochondrial dysfunction, which can lead to neurotoxicity.
• Gene expression: APOE4 can translocate to the nucleus, where it regulates the expression of genes involved in aging, inflammation and apoptosis.
• Regulates many bodily functions: APOE regulates brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation and mitochondrial function.

How Does the APOE4 Gene Cause Alzheimer’s Disease?

Certain genes can increase the chances of developing Alzheimer’s, while others make it nearly certain, though these are rare. The most common gene linked to Alzheimer’s after age 65 is the APOE gene, which has three types:

1. APOE2 – Rare and lowers Alzheimer's risk.
2. APOE3 – The most common type, with no effect on risk.
3. APOE4 – Increases Alzheimer’s risk and can worsen symptoms if the disease develops.

As an APOE4 carrier, inheriting one or two copies of APOE4 from parents raises Alzheimer’s risk, but having these genes doesn’t guarantee someone will get the disease. Many people with the gene don’t develop Alzheimer’s, while others without it do. This suggests other factors like lifestyle, environment and background also play a role.

About 25 per cent of people carry at least one APOE4 gene, the biggest known genetic risk for late-onset Alzheimer’s. Interestingly, APOE4 carriers often perform better on cognitive tests in midlife, though their risk for dementia and cognitive decline increases in older age.

Ongoing research is exploring more genes linked to Alzheimer’s, such as ABCA7, CLU and CR1, which may eventually help in developing new treatments and prevention strategies.

Further Reading: All About Nootropics and Brain Health Supplements

What percentage of people with APOE4 get dementia?

For people of European descent, having two copies of a gene variant called APOE4 is one of the strongest genetic risk factors for Alzheimer's disease. Around 60 per cent of APOE4 homozygotes — those with two copies of this gene — are likely to develop Alzheimer's by age 85. Though they make up only 2 per cent of the population, they represent about 15 per cent of Alzheimer’s Disease cases.

A study led by researchers in Barcelona examined data on over 3,200 people with different APOE gene types. Results showed that almost all APOE4 homozygotes had brain changes related to Alzheimer’s by age 55. Alzheimer’s Disease symptoms, like mild memory issues, typically began around age 65, with dementia diagnosis around age 74, about 7–10 years earlier than in those without APOE4.

The predictable pattern of Alzheimer’s Disease development in APOE4 homozygotes is similar to that in other genetically linked forms of Alzheimer’s, suggesting that Alzheimer's in these people is largely driven by genetics. This highlights the need for specific research into diagnosis and treatment for APOE4 homozygotes and studies in more diverse populations beyond those of European descent.

Does DHA Help with Alzheimer’s?

Identifying factors affected by APOE4 — like DHA metabolism — could help develop treatments for neurodegeneration.

DHA, an omega-3 fat, supports brain cell membranes and signalling. It is especially important for people with APOE4, who are more prone to neuron damage. Research suggests that APOE4 carriers are more vulnerable to DHA deficiency than others, meaning that DHA-rich diets might benefit them more. The thing is, studies show that APOE4 carriers metabolise DHA faster, making it harder for the brain to retain DHA.

APOE4 carriers may have a lower supply of DHA to the brain because of faster clearance from the bloodstream, reduced transport across the blood-brain barrier and changes in how DHA is processed inside the brain.

Further Reading: Supplements to Boost Focus and Concentration

Mixed Results on DHA Supplements

Observational studies and clinical trials have produced inconsistent results. Some studies show DHA supplements help APOE4 carriers, while others show benefits only for non-carriers. In the ADCS-DHA trial, DHA supplements didn’t improve memory for most patients, although there were hints of benefits for non-APOE4 carriers. APOE4 carriers showed lower DHA levels in the brain and blood even after 18 months of supplementation, suggesting they may need higher doses or more frequent dosing to see any benefits.

LPC-DHA and Neuroprotection

LPC-DHA (a form of DHA transported into the brain by Mfsd2a) could increase brain DHA levels more effectively than traditional DHA supplements. Higher brain DHA improves neuron function and memory and may protect against neurodegenerative diseases. Research also shows that krill oil, which contains high LPC-DHA levels, can improve memory in APOE4 mice and potentially benefit patients with brain diseases.

Interestingly, mice given krill oil diets showed improved memory, though they also gained more weight and ate more. It's unclear how these changes in weight or diet preferences might affect brain function in the long run, so more research is needed.

Xandro’s LPC Neuro

For scientifically validated brain and mind support, Xandro’s LPC Neuro may help. It uses Lysoveta™, an LPC-bound DHA/EPA, which is the first supplement of its kind that can actually cross the blood-brain barrier. This way, the brain can absorb the essential omega-3 fatty acids it needs and might benefit individuals with the ApoE4 gene, who are at higher risk of Alzheimer’s.

It's been clinically tested, so it’s free from heavy metals and contaminants and is in the form of high-quality soft gel capsules that are easy to take. Just take one a day to improve your brain and eye health!

End Note

While genetics do play a role in developing conditions like Alzheimer’s Disease, LPC-DHA-rich diets, and now supplements, offer a promising strategy to boost brain DHA levels and protect against age-related brain decline, especially for APOE4 carriers.

Learn more about Xandro’s LPC Neuro or keep yourself informed about your health and longevity in our blogs!