Introduction
Apolipoprotein E is a protein that is essential for fat metabolism in the body. The apolipoprotein E gene has various variants, and they cause various diseases. These genes have been found to be associated with Alzheimer's disease, Parkinson's disease, atherosclerosis, and kidney diseases.
What Is Apolipoprotein E (APOE)?
The apolipoprotein E (APOE) gene gives the necessary instructions for the production of a protein known as apolipoprotein E. In the body, this protein interacts with lipids to create substances known as lipoproteins. This lipoprotein plays an important role in the transport of fats and cholesterol. Cholesterol and other fats are transported through the bloodstream in a package by lipoproteins. Maintaining normal cholesterol levels is crucial for avoiding cardiovascular diseases, such as heart attacks and stroke, which affect the heart and blood vessels.
The APOE gene exists in three slightly distinct variants. E2, E3, and E4 are the three main genes. Out of all these variants, the most common gene is E3. In addition, more than half of the population carries the most prevalent gene, E3.
What Are the Disorders Linked With Apolipoprotein E?
Apolipoprotein E is linked with the following disorders:
-
Alzheimer’s disease.
-
Kidney disorders.
-
Cardiovascular disorders.
How Is Apolipoprotein E Linked to Alzheimer’s Disease?
Apolipoprotein E helps in the transportation of cholesterol and fat in the blood. The gene for apolipoprotein E has three common forms: APOE2, APOE3, and APOE4. Out of these forms, APOE4 was recognized as a genetic risk factor for Alzheimer's disease in 1993. In addition to this, one-third of cases of Alzheimer's disease (AD) may be caused by the APOE4 gene.
Alzheimer's disease is a progressive brain disease that results in dementia (loss of memory, judgment, and functional abilities). People over 65 years of age are more likely to develop the late-onset version of Alzheimer’s disease. A person's risk of acquiring the disease rises if they inherit one copy of the APOE4 gene; if they inherit two copies, their risk rises even further. In addition, the APOE4 gene may also be linked to an earlier onset of memory loss and other symptoms in Alzheimer's disease patients compared to those who do not carry this gene.
What Is the Importance of the Apolipoprotein E Blood Test?
The apolipoprotein E blood test is used to examine an individual’s deoxyribonucleic acid (DNA) to determine which APOE genes are present. In this test, DNA is taken out from the given blood sample, and assessments of APOE genes are done. From each parent, an individual receives either an E2, E3, or E4 gene. Therefore, those individuals who have one or two APOE4 genes may be at a higher risk of getting Alzheimer's disease than people who do not have APOE4 genes.
Although the presence of E4 genes increases the risk of Alzheimer’s disease, it is not necessary that every person with the E4 gene will develop this disease. It has been seen that some people who carry the E4 gene will never develop AD, while others who do not carry the gene will eventually get AD. However, about one-third of all cases of AD are linked to APOE4.
What Are the Disadvantages of the APOE Test?
The APOE test is not a confirmatory test for Alzheimer's disease. From this test, only the increased risk of acquiring the disease can be anticipated. Additionally, the APOE test can not help in determining the treatment plan for AD. Currently, this test primarily serves as a research tool for additional study into the causes, symptoms, treatments, and prevention of Alzheimer's disease.
How Is Apolipoprotein E (APOE) Linked to Kidney Disorders?
Apolipoprotein E can cause some kidney disorders, such as glomerular disorders. Glomerular disorders are conditions that affect the glomerulus of the kidney. These glomeruli are the relatively tiny network of blood vessels that remove waste and extra fluids from the blood and are known as cleaning units of the kidney. The glomerular disorders caused by apolipoprotein E are APOE2 homozygote glomerulopathy and lipoprotein glomerulopathy (LPG).
APOE2 homozygote glomerulopathy occurs in individuals with homozygous APOE2/2. In contrast, lipoprotein glomerulopathy is predominantly associated with heterozygous APOE mutations surrounding the low-density lipoprotein-receptor binding site.
Both these kidney disorders occur due to lipoprotein degeneration depending on the APOE gene mutation, and they frequently advance into end-stage kidney disease. As a result, no effective treatment has yet been identified.
How Is Apolipoprotein E (APOE) Linked to Parkinson's Disease?
Parkinson's disease manifests as slowness of movement, resting tremors, stiffness, and loss of balance or postural instability. This disease is the second most prevalent neurodegenerative illness and affects one-fourth of the population, which may be due to a major genetic component. Numerous pieces of evidence, including the cognitive deterioration of Parkinson's disease, clinical similarities, and cerebrospinal fluid biomarkers, indicate a link between the APOE genotype and Parkinson's disease.
In Parkinson’s disease, the genetic variation of APOE has been found to be associated with dementia (loss of memory) and cognitive decline that occur in this disease. Some studies demonstrated that the APOE4 gene plays an important role in the development of dementia in Parkinson’s disease.
How Is Apolipoprotein E (APOE) Linked to Cardiovascular Disease?
The risk of cardiovascular disease has been found to be associated with APOE genes. Atherosclerosis, a buildup of fatty deposits and scar-like tissue in the lining of the arteries, is more likely to occur in individuals who have at least one copy of the APOE4 gene. In addition, atherosclerosis can increase the risk of heart attack and stroke because of the narrowing of arteries.
What Are the Other Disorders Linked to Apolipoprotein E?
Apart from Alzheimer's disease, Parkinson's disease, and atherosclerosis, a rare condition known as hyperlipoproteinemia type III can occur because apolipoprotein E. APOE genes increase the risk of getting hyperlipoproteinemia III in an individual. In studies, it has been found that the majority of people with this disease have two copies of the APOE2 gene. Therefore, researchers have concluded that the E2 gene is responsible for the occurrence of hyperlipoproteinemia type III.
Hyperlipoproteinemia type III is associated with high blood levels of cholesterol, triglycerides, and beta-very low-density lipoproteins (beta-VLDLs, or bad cholesterol), which transport cholesterol and lipoproteins in the bloodstream. These conditions can result in the formation of atherosclerosis (narrowing of arteries due to fat deposition) and xanthomas, which are tiny, yellow skin growth.
Conclusion
Apolipoprotein E protein is a key protein that is required for brain function, especially cognitive function. They have three variants: E4, E3, and E2 genes. The most dangerous of the three frequent APOE genes are the E4 genes, followed by the E3 gene and the E2. These genes can cause various disorders, such as kidney disorders and heart diseases like atherosclerosis, Parkinson's disease, and Alzheimer's disease.
