Apolipoprotein (apo) E was initially identified as a key determinant in lipoprotein metabolism and cardiovascular disease, but it has since come to be recognised as a crucial molecule in several biological processes unrelated to its lipid transport function, such as Alzheimer's disease and cognitive function, immunoregulation, and perhaps even infectious diseases.

Apolipoprotein- E Test Overview

Apolipoprotein (apo) E was initially identified as a key determinant in lipoprotein metabolism and cardiovascular disease, but it has since come to be recognised as a crucial molecule in several biological processes unrelated to its lipid transport function, such as Alzheimer's disease and cognitive function, immunoregulation, and perhaps even infectious diseases.

Apolipoprotein- E in short APOE and what it means for your health

The transport of cholesterol between various tissues and cells is one of the numerous crucial functions of the APOE protein. Different APOE alleles produce proteins that handle this transport function in different ways. As demonstrated by the fact that APOE -deficient humans have dramatically higher plasma cholesterol levels and are more likely to develop atherosclerosis, this protein is an important regulator of plasma lipid levels (for a review, see 1). By encouraging the removal of triglyceride (TG)-rich lipoproteins from circulation, apoE plays a significant role in lowering plasma cholesterol levels, which in turn has an anti-atherogenic effect 2, 3. Three common isoforms of human apoE (apoE2, apoE3, and apoE4) exist, and this polymorphism influences disease risk in carriers.

Apolipoproteins E, which make up the structural components of lipoprotein particles, take part in the synthesis, secretion, processing, and metabolism of these proteins. Apolipoproteins play crucial functions in the metabolism of blood lipids.

What exactly is the Apolipoprotein-E test?

An Apolipoprotein-E test is often performed to check whether specific genes are impacting your present levels of triglycerides and cholesterol. This test is frequently necessary to assess your risk for heart disease and to evaluate whether you are susceptible to Alzheimer's disease. You should see your doctor right soon to get tested for Alzheimer's disease if you have a family history of the condition or if one of your loved ones has been diagnosed with it. It makes sense for you to get yourself tested as soon as possible because Alzheimer's disease is thought to be genetically and hereditarily inherited.

In most cases, the clinical diagnosis of Alzheimer’s disease, AD is based on the presence of slowly progressing dementia symptoms, the discovery of substantial cerebral cortical atrophy on neuroimaging, and the exclusion of alternative dementia-causing conditions. Amyloid positron emission tomography (PET) imaging, as well as measures of amyloid and tau in cerebral spinal fluid, are further investigations that can help with a clinical diagnosis of Alzheimer’s disease. 

Beta (β)-amyloid plaques and intraneuronal neurofibrillary tangles containing tau protein are hallmark neuropathologic features that can only be found post-mortem and used to confirm a diagnosis of Alzheimer's disease (AD). In addition to APOE, other genes have been linked to late-onset AD, but their influence on disease risk is negligible. Genetic testing to determine the risk of developing late-onset AD is not yet proven to be clinically useful.

Who Needs Apolipoprotein-E test?

The apolipoprotein-E polymorphism alters how many diseases are susceptible. However, it is particularly well-known for its part in atherosclerotic arterial disease and neurodegenerative illnesses. The effects of apoE on reverse cholesterol transport, platelet aggregation, and oxidative processes are anticipated to have an impact on the overall atherogenic potential associated with the modification of lipoprotein metabolism. These effects are allele- and gender-dependent. A recent meta-analysis fully validates the existence of the 4 alleles as a major risk factor for coronary artery disease notwithstanding the context dependence.  The association between Apolipoprotein-E and atherosclerosis in humans has been partially explained by several processes. However, certain Apolipoprotein-E -mimicking peptides that increase LDL clearance is currently being investigated in animals for possible clinical uses.

Although APOE genotyping does not offer enough sensitivity or specificity to be used by itself as a diagnostic test for Alzheimer's disease, it does increase the specificity of the diagnosis when combined with clinical criteria.

People facing the below symptoms need to have an Apolipoprotein-E test:

• Memory loss that interferes with daily life—forgetting facts recently learnt. Normal ageing can cause this, but people typically remember the information afterwards. This involves forgetting significant dates or events, using memory aids, and repeatedly asking for the same information.
• Preparing or addressing problems with difficulty, such as remembering to pay your bills on time.
• Difficulties carrying out routine chores, including forgetting how to travel to a known place.
• Confusion regarding time or location—forgetting the time, where you are, or how you got there.
• Increasing trouble with distance judgement or reading.
• Issues when speaking or writing—forgetting words, using the same phrase repeatedly, or having vocabulary issues.
• Becoming more prone to losing things and being unable to logically go back in time to find them.

Preparation & procedure of Apolipoprotein-E test 

The APOE test is frequently used to detect your vulnerability to Alzheimer's disease as well as to assess your current state of cardiovascular health. This is why you should see your doctor right away; he will first check your medical history, including that of your family, and then arrange an APOE test as soon as possible to discover if you are prone to Alzheimer's disease. The APOE test should also provide a thorough picture of your cardiac health, particularly by determining which genes are now affecting your cholesterol and triglyceride levels.

The test procedure 

• Your physician will perform a venepuncture and collect a small sample of your blood in a sterile container.
• Depending on which genes are to be checked, your doctor may advise that you follow a diet restriction.
• You must ensure that you strictly adhere to your doctor's advice.
• The collected sample is then tagged and processed at the laboratory, where it will be fully sequenced to study and analyse the impact of specific genes on your current cholesterol and triglyceride levels.
• To determine your susceptibility to Alzheimer's, dementia, depression, and other forms of degenerative diseases.

Apolipoprotein-E Test Results 

People with one or more APOE e4 copies with Alzheimer's disease (AD) symptoms are more likely to have AD. It should not be used to screen asymptomatic persons or their family members because it is not a diagnostic test for AD. Many people with the APOE e4 allele will never acquire Alzheimer's disease. Only over 60% of patients with late-onset AD will carry APOE e4 alleles, even in symptomatic individuals. APOE genotyping can only offer more details about a person with dementia, even though Alzheimer’s specialists may use it clinically. Only after a person has passed away and their brain matter has been examined can an Alzheimer’s disease diagnosis be made with certainty.

There are many persons with AD who are e4 negative, however, most people with APOE e4 will never get AD in terms of lifetime risk. 

There are no definitive diagnostics for diagnosing Alzheimer's disease during one's lifetime. However, by ruling out other potential causes of dementia and evaluating for genetic susceptibility to AD with APOE genotyping as extra information in conjunction with tau protein and beta-amyloid tests, healthcare practitioners can make a reasonably reliable clinical diagnosis of AD.