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Another Role for ApoE

While Alzheimer's disease is strongly associated to advancing age, there is still considerably more to be known regarding its etiology, progression, and treatment options. What is apolipoprotein E and how might it evolve to a better understanding of Alzheimer's disease at diagnostic, preventative, and therapeutic levels?

While Alzheimer’s disease is strongly associated to advancing age, there is still considerably more to be known regarding its etiology, progression, and treatment options. But even amidst the uncertainty of what exactly causes Alzheimer’s disease, researchers link it to genetic risk factors and may have found another role for apolipoprotein E. But what is apolipoprotein E and how might it evolve to a better understanding of Alzheimer’s disease at diagnostic, preventative, and therapeutic levels?

What Is ApoE?

Also known as apoE, apolipoprotein E is a glycoprotein made out of amino acids (the building blocks of protein) and located on chromosome 19. There are three primary variations of the apoE gene, also known as alleles, and include apoE2, E3, and E4. Each person has two copies of the gene and the combination determines your apoE genotype, which may consist of E2/E2, E2/E3, etc. Though the varying alleles act differently, apoE’s primary function is to transport fats (or lipids) in the bloodstream from one cell to another. Whereas apoE is present in several organs, it is mostly expressed in the liver, with the brain following right after.

Understanding Alzheimer’s Disease

According to the Alzheimer’s Association, Alzheimer’s disease (AD) is the most common form of dementia, a general term to describe memory loss and other compromised intellectual abilities serious enough to interfere with daily life.

While cognitive decline often comes with advancing age, Alzheimer’s disease is not considered a normal part of aging, yet is the greatest risk factor for developing AD. The condition has no known cure to date and is progressive and irreversible, ultimately worsening over time and taking the lives of those affected. And with Alzheimer’s being the sixth leading cause of death in the United States, researchers work diligently to better understand the root of the condition and discover longstanding treatment and preventive methods. However, health experts do recognize individuals with AD display a greater formation of beta-amyloid plaques and tau tangles in the brain, as well as neuronal losses and brain degeneration and inflammation.

Alzheimer’s disease is divided into two types, including early-onset and late-onset (LOAD). Early-onset occurs between the ages of 30 and 60 years and represents less than five percent of all people with AD. The cause of early-onset is unknown at the time, although most cases are inherited and specifically known as familial Alzheimer’s disease (FAD), which is caused by a genetic mutation. Most of AD cases are late-onset and developed after age 60 years. Researchers speculate LOAD is mostly 60 to 80 percent inherited, whilst other genetic and environmental factors contribute to its onset, progression, and severity.

Linking Apolipoprotein E and Alzheimer’s Disease

Newly discovered over the past decade or two, apolipoprotein E is the only known gene related to late-onset Alzheimer’s disease at this time. Numerous studies have confirmed possessing the E4 allele is the strongest genetic risk factor for both Alzheimer’s disease; one copy of E4 can increase AD by two to three times while two copies, or a homozygous pattern (E4/E4), is associated with the highest likelihood of developing late onset AD by 12 percent.

Researchers speculate the link relates to apoE’s function of carrying cholesterol to and from the brain, along with clearing beta-amyloid deposits. Compromised or diminished function of the gene may cause excessive amyloid build-up, a phenomenon consistently witnessed amongst individuals with AD. Furthermore, the apoE-4 is present in about 40 percent of all people with LOAD. Even outside of the brain, apoE-4 has shown to increase the risk of atherosclerosis (hardening and thickening of artery walls) and stroke, two major risk factors of Alzheimer’s disease. ApoE-4 may also contribute to neuronal degeneration, along with causing inflammation in the brain.

Genetic Testing of Apolipoprotein E

It is important to realize while carrying apoE-4 increases the risk of Alzheimer’s disease, it does not designate an absolute current or future diagnosis. And although a blood test can help determine which apoE alleles a person inherited, it cannot predict nor guarantee who will develop Alzheimer’s disease. In fact, the recommendation for genetic testing is not based merely for diagnosing AD, but rather advancing discovery of AD development, preventative measures, and treatment options.

Ultimately, researchers are still working towards resolving whether or not the apoE-4 allele influences AD development via a gain of toxic function, loss of protective function, or an arrangement of both phenomena. The uncertainty divides researchers to approach two different therapeutic strategies, one aiming to lessen potential risky effects of apoE-4 by altering its structure and the other attempting to restore the physiological roles of apoE/apoE-4 by increasing its function. Nonetheless, developing effective and therapeutic strategies surrounding apoE is predominately in hopes to lessen the risk and severity of Alzheimer’s disease in the (hopefully near) future.

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