APOE gene: MedlinePlus Genetics (2023)

FAQs

What is the APOE gene? ›

One well-known gene that influences Alzheimer's risk is the apolipoprotein E (APOE) gene. The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer's.

In peripheral tissues, ApoE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism in an isoform-dependent manner. ApoE4 is associated with hyperlipidaemia and hypercholesterolemia, which lead to atherosclerosis, coronary heart disease and stroke.

About 25% of people carry one copy of APOE4, and 2 to 3% carry two copies. APOE4 is the strongest risk factor gene for Alzheimer's disease, although inheriting APOE4 does not mean a person will definitely develop the disease. The study suggests that dementia may be caused by lipid imbalances in brain cells.

The APOE gene provides the blueprint for a protein that carries cholesterol in the blood. Everyone inherits one form of the APOE gene — e2, e3 or e4 — from each parent. The e3 form is the most common, with about 60% of the U.S. population inheriting e3 from both parents. The e2 and e4 forms are much less common.

But not everyone who has one or even two APOE e4 genes gets Alzheimer's disease. And many people who don't have an APOE e4 gene get the disease. That suggests that the APOE e4 gene increases risk but is not a cause.

The expression and harmful effects of the ApoE4 gene appear to be downregulated by eating a low-glycemic load (GL) diet or a more ketogenic diet with specific Mediterranean-style food choices including fatty fish, cruciferous vegetables, olive oil, and low alcohol consumption.

Overall, our results indicate that the use of statins may benefit all AD subjects and may be most beneficial in subjects with an ApoE4/ApoE4 genotype.

A single APOE4 allele increases this risk up to 4.4, and two copies of APOE4 increase this to 19.3! The protective effect of the APOE2 allele can also be seen, a single copy of APOE2 reduces the risk down to 0.3, and can mitigate for an APOE4 allele, effectively keeping the risk neutral (1.1).

Background. The three main alleles of the APOE gene (ε4, ε3 and ε2) carry differential risks for conditions including Alzheimer's disease (AD) and cardiovascular disease.

Does ApoE4 affect cholesterol? ›

Cholesterol dysregulation by ApoE4 could lead to cell type-specific functional abnormalities in the brain such as Aβ upregulation and impaired synaptic function in neurons, reduced synapse prunning activity in astrocytes, impaired remyelination in oligodendrocytes, and Aβ accumulation and inflammatory response in ...

Family history

Those who have a parent, brother or sister with Alzheimer's are more likely to develop the disease. The risk increases if more than one family member has the illness. When diseases tend to run in families, either heredity (genetics), environmental factors, or both, may play a role.

However, for people with abnormal cholesterol metabolism, such as those with APOE4, this revised guideline does not apply; limiting fat, saturated fat and cholesterol-rich foods, such as eggs, shellfish, red meat and dairy, is critical for these people to minimize their risk of heart disease.

The apolipoprotein E ε4 (APOE*ε4) allele is among the most robust risk factors for cognitive decline, especially among people of European ancestry. The allele is more common among those of African ancestry, but has a smaller—though still important— relationship with cognitive decline in this population.

APOE3 is the most common allele and doesn't seem to influence risk. The APOE4 allele, present in approximately 10-15% of people, increases the risk for Alzheimer's and lowers the age of onset.

Administration: The examiner reads a list of 5 words at a rate of one per second, giving the following instructions: “This is a memory test. I am going to read a list of words that you will have to remember now and later on. Listen carefully. When I am through, tell me as many words as you can remember.

Hemsworth learned that he has two copies of the APOE4 gene (one from each of his parents), which is known to increase the risk of Alzheimer's. His revelation has brought renewed attention to the role of genes in Alzheimer's disease.

There are no approved predictive genetic tests for the most common form of Alzheimer's disease. However, regional genetics clinics offer testing for people whose family history of dementia suggests they might carry one of the causative mutations for inherited Alzheimer's or frontotemporal dementia.

The pooled results showed that ApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with a high risk of COVID-19 (P = 0.0003, OR = 1.44, 95% CI 1.18–1.76) (Fig. 2A). For the disease severity, a total of 573 COVID-19 cases and 324752 controls from five studies were analyzed.

There is some evidence that vegetarians have a lower risk of dementia [157] and no evidence about the association of a vegan diet with dementia.

How does APOE4 affect the brain? ›

APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease.

Narcotics such as hydrocodone, oxycodone and morphine; muscle relaxants such as cyclobenzaprine, carisoprodol; NSAIDs such as ibuprofen, naproxen should be avoided if possible. If these medications must be used, they should be used at the lowest effective dose for the shortest duration to minimize adverse effects.

There were some early case reports that reported associations between statin use and reduced cognition. In addition, the US Food and Drug Administration warned about these possible adverse effects in 2012.

One genetic factor that is far and away the largest predictor of developing Alzheimer's – the E4 allele of the human apolipoprotein E gene (APOE4). Carrying one copy of the E4 allele is associated with a 47% lifetime risk of developing Alzheimer's, while carrying two copies increases lifetime risk to 91%.

In conclusion, our data show that carrying the APOE ɛ4 allele leads to an increased chance of cognitive impairment and an early death.

Older age does not cause Alzheimer's, but it is the most important known risk factor for the disease. The number of people with Alzheimer's disease doubles about every 5 years beyond age 65. About one-third of all people age 85 and older may have Alzheimer's disease.

In a comprehensive review of dementia prevention strategies, a low-carbohydrate diet or a low-glycemic index diet is recommended for people with the APOE4 variant [5]. Omega-3 fatty acids such as docosahexaenoic acid (DHA), rich in salmon, mackerel, and other fatty fish, are building blocks of the brain.

We demonstrate that the removal of neuronal APOE4 has wide-ranging beneficial effects, leading to drastic reductions (1) in the accumulation and spread of pathological tau throughout the hippocampus; (2) in neurodegeneration and hippocampal neuron loss; (3) in myelin deficits and depletion of oligodendrocytes and OPCs; ...

Background. Approximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer's disease.

How does APOE affect mental health? ›

APOE ε4 allele increased the depression risk; depressive patients carrying APOE ε4 allele had more severe depressive symptoms.

The most widely used CSF biomarkers for Alzheimer's disease measure beta-amyloid 42 (the major component of amyloid plaques in the brain), tau, and phospho-tau (major components of tau tangles in the brain, which are another hallmark of Alzheimer's).

Apolipoprotein E-e4 (APOE4),

discovered in 1993, is the first gene variation found to increase risk of Alzheimer's and remains the risk gene with the greatest known impact. Having this mutation, however, does not mean that a person will develop the disease.

Carriers of the APOE4 allele (20–25% whites) are at increased risk of CVD, in part attributable to the modestly higher plasma LDL-cholesterol and triglyceride concentrations in this subgroup (6, 7).

APOE2 genes are generally associated with low LDL levels. On the other hand, the E4 variant is characterized by faster cholesterol metabolism. This typically results in higher LDL and total cholesterol levels at even low body mass indexes for those with APOE4 genes.

ApoE2 and apoE4 increase the risk for heart disease: apoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors), and apoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors).

Studies show that dementia risk is lowest in people who have several healthy behaviours in mid-life (aged 40–65). These behaviours include: ∎regular mental, physical and social activity ∎not smoking ∎drinking alcohol only in moderation ∎keeping a healthy diet.

People who live a healthy lifestyle, especially from mid-life (age 40–65) onwards, are less likely to develop Alzheimer's. This includes not smoking, not drinking too much alcohol, and eating a healthy balanced diet.

Many foods in the Western diet have been identified as risk factors for dementia and Alzheimer's, including red and processed meats, refined grains, sweets, and desserts. Excess alcohol intake, saturated fatty acids, and foods with a high number of calories are also risk factors for Alzheimer's.

What's the worst food for Alzheimer's? ›

Avocados

Avocados are full of healthy monounsaturated fats, just like olive oil. People who eat more monounsaturated fats (and omega-6 polyunsaturated fats) are less likely to develop Alzheimer's disease and dementia.

The 23andMe test evaluates whether an individual has the APOE-e4 Alzheimer's risk gene, but not deterministic genes for Alzheimer's.

But not everyone who has one or even two APOE e4 genes gets Alzheimer's disease. And many people who don't have an APOE e4 gene get the disease. That suggests that the APOE e4 gene increases risk but is not a cause.

APOE4 is the strongest risk factor gene for Alzheimer's disease, although inheriting APOE4 does not mean a person will definitely develop the disease.

Overall, our results indicate that the use of statins may benefit all AD subjects and may be most beneficial in subjects with an ApoE4/ApoE4 genotype.

In peripheral tissues, ApoE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism in an isoform-dependent manner. ApoE4 is associated with hyperlipidaemia and hypercholesterolemia, which lead to atherosclerosis, coronary heart disease and stroke.

APOE3-Jac was linked to reduced risk for AD and dementia with Lewy bodies (DLB) [17, 18]. A recent study showed that apoE3-Jac promotes healthy brain aging and decreases amyloid deposition and associated toxicity by reducing apoE self-association and increasing lipidation [17].

APOE plays a vital role in the metabolism of amyloid β (Aβ). APOE2, APOE3, and APOE4 proteins can each directly bind with Aβ, forming APOE/Aβ complexes that alter Aβ clearance, aggregation, and the formation of senile plaques [36].

ApoE-containing lipoprotein particles may sequester Aβ and modulate the cellular uptake of an apoE-Aβ complex by receptor-mediated endocytosis. Alternatively, apoE may modulate Aβ removal from the brain to the systemic circulation by transport across the blood-brain-barrier.

What is the gene that causes dementia? ›

The most well-known risk variants for dementia are for Alzheimer's disease. These are in the apolipoprotein E gene – more commonly known as the 'APOE' gene. Over 20 other genetic variants have also been identified as risk variants for Alzheimer's disease.

APOE-e4 is the first risk gene identified and remains the gene with strongest impact on risk. Researchers estimate that between 40-65% of people diagnosed with Alzheimer's have the APOE-e4 gene.

Cholesterol dysregulation by ApoE4 could lead to cell type-specific functional abnormalities in the brain such as Aβ upregulation and impaired synaptic function in neurons, reduced synapse prunning activity in astrocytes, impaired remyelination in oligodendrocytes, and Aβ accumulation and inflammatory response in ...

The three main alleles of the APOE gene (ε4, ε3 and ε2) carry differential risks for conditions including Alzheimer's disease (AD) and cardiovascular disease.

APOE and Alzheimer disease: a major gene with semi-dominant inheritance.

The cognitive boost conferred by APOE4 in younger people could be enough to explain its continued presence in the gene pool. For example, the boost it gives to short-term memory could have been a strong advantage when our hunter-gatherer ancestors were out looking for food.

The causes probably include a combination of age-related changes in the brain, along with genetic, environmental, and lifestyle factors.

Studies of family history say that if you have a close relative who has been diagnosed with Alzheimer's disease—the most common form of dementia in older adults—your risk increases by about 30%. This is a relative risk increase, meaning a 30% hike in your existing risk.