Alzheimer’s Disease, ApoE4 & Risk Detection

Alzheimer’s disease touches all of us, whether directly through an affected loved one or through its frequent presence in the news. Alzheimer’s disease is a progressive neurodegenerative disorder characterised by cognitive decline, memory loss, and functional impairments. It is the most common cause of dementia, affecting millions of individuals worldwide ¹ and posing significant challenges to healthcare systems. As the global population ages, the prevalence of Alzheimer’s disease is expected to rise, highlighting the urgent need for effective diagnostic and therapeutic strategies.

The current methods used to diagnose Alzheimer’s disease consist of clinical assessment and supporting neuroimaging techniques which can be expensive and, in some cases, fail to provide a definitive diagnosis at the early stages required to facilitate timely intervention and slow disease progression.

With novel therapeutics which aim to slow the progression of Alzheimer’s Disease achieving approval in the United States and being considered for approval in other countries, diagnostics which can identify those at risk of developing this disease are more important than ever. Biomarkers have emerged as vital tools in the early detection and risk assessment of Alzheimer’s disease. Among these, the apolipoprotein E gene (ApoE) has garnered significant attention. The apolipoprotein E protein (ApoE) exists in three common isoforms: ApoE2, ApoE3, and ApoE4. These isoforms combine to form six common genotypes in the general population. Notably, the presence of the ApoE4 allele is associated with a significantly increased risk of developing Alzheimer’s disease.

The Randox ApoE4 Array marks a significant advancement in Alzheimer’s disease biomarkers. This quick and sensitive blood test allows direct ApoE4 genotyping, eliminating the need for traditional molecular techniques. With its fast and accurate results, healthcare providers can efficiently assess an individual’s genetic risk for Alzheimer’s disease.

In this article, we present a summary of our latest whitepaper: Alzheimer’s Disease, ApoE4 & Risk Detection in which we explore the critical role of ApoE genotyping in Alzheimer’s Disease, the innovative technology behind the Randox ApoE4 Array, and its implications for clinical practice. You can download this whitepaper through the link below.

Apolipoprotein E and Alzheimer’s Risk

The ApoE gene transcribes a 229 amino acid protein which primarily functions to mediate lipid transport in the brain and periphery. ApoE is also involved in immune modulation, synapse regeneration, and the clearance/degradation of amyloid-β, a peptide crucial to the development of Alzheimer’s disease².

There are 3 common isoforms of the human ApoE, differentiated through single nucleotide polymorphisms (SNPs) at amino acid positions 112 and 158²:

These three isoforms combine to produce six common genotypes: E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, and E4/E4. Each genotype is associated with a different level of risk for developing Alzheimer’s disease, with the ApoE4 and ApoE2 isoforms presenting the highest³ and lowest risk ⁴ respectively.

The structural differences among ApoE isoforms affect their ability to bind lipids, receptors, and amyloid-β, influencing cognitive decline. ApoE2 and ApoE3 bind effectively to HDL (High density lipoprotein), while ApoE4 binds to VLDL (Very low-density lipoprotein), resulting in poor lipidation and toxic aggregates^1,2. Cholesterol is crucial for brain function, supporting membrane integrity, signal transduction, and amyloid-β regulation. The interaction of ApoE with amyloid-β regulates amyloid plaque formation, influencing Alzheimer’s disease onset. Cholesterol must be converted to 24S-hydroxycholesterol to cross the blood-brain barrier. Poor cholesterol and phospholipid transport by ApoE4 increases the risk of late-onset Alzheimer’s disease in E4 carriers².

Randox ApoE Array

The Randox ApoE4 Array is a rapid and highly sensitive blood test that facilitates direct ApoE4 genotyping without the need for traditional molecular techniques. It measures both total ApoE and ApoE4 protein levels directly from a plasma sample, using the ApoE4/total ApoE ratio to classify the ApoE4 status as negative or positive. Additionally, the array can distinguish between heterozygous and homozygous individuals among ApoE4 positive samples, aiding in the assessment of Alzheimer’s disease risk.

Using Randox proprietary chemiluminescent biochip-sandwich immunoassays, the array provides accurate results within three hours from a minimally invasive plasma sample. This method has shown 100% concordance with genotypes achieved through restriction fragment length polymorphism (RFLP) in two separate centres⁵. Compared to other methods like isoelectric focusing, mass spectrometry, bead-based immunoassay, Sandwich ELISA, and PCR, the Randox ApoE Array offers advantages in speed, simplicity, and automation.

Clinical Implications

The Randox ApoE Array offers significant benefits for managing Alzheimer’s disease through early detection and personalised treatment plans. This minimally invasive blood test identifies individuals at higher genetic risk for Alzheimer’s Disease enabling:

• Timely Interventions: Early identification allows for preventive measures and lifestyle modifications, such as cognitive training and increased physical activity, to delay symptom onset.
• Regular Monitoring: High-risk individuals can be monitored for cognitive changes, enabling early intervention for mild cognitive impairment.

Personalised Treatment Plans

Accurate ApoE genotyping supports personalised treatment:

• Targeted Therapies: ApoE phenotype informs the selection of therapies, especially for ApoE4 carriers.
• Risk Stratification: Patients can be stratified by genetic risk for targeted preventive measures.
• Optimised Medication: Genotype information guides medication choices, enhancing efficacy.
• Family Counselling: Genotyping aids family counselling, advising on preventive measures and monitoring.

Conclusions

The Randox ApoE Array represents a groundbreaking advancement in the early detection and management of Alzheimer’s disease. By providing a rapid, highly sensitive, and minimally invasive method for ApoE genotyping, it empowers healthcare providers to implement timely interventions and personalised treatment plans. This innovative approach not only enhances the accuracy of Alzheimer’s risk assessment but also supports the development of targeted therapies and optimised medication regimens, ultimately improving patient outcomes.

Early detection of Alzheimer’s disease allows for proactive measures that can delay the onset of symptoms, while personalised treatment strategies tailored to an individual’s genetic profile offer a more effective management approach. Furthermore, the array’s capability to provide real-time insights into a patient’s disease stage makes it an invaluable tool in the fight against Alzheimer’s disease.

For a deeper understanding of the critical role of ApoE genotyping in Alzheimer’s disease and the innovative technology behind the Randox ApoE Array, we invite you to download our comprehensive whitepaper be clicking on the image below.  You can also visit our website to access this and other valuable resources and to learn more about the Randox ApoE4 Array.

References

1. Raulin AC, Doss S V., Trottier ZA, Ikezu TC, Bu G, Liu CC. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Mol Neurodegener. 2022;17(1):72. doi:10.1186/s13024-022-00574-4
2. Husain MA, Laurent B, Plourde M. APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics. Front Neurosci. 2021;15. doi:10.3389/fnins.2021.630502
3. Qian J, Wolters FJ, Beiser A, et al. APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts. PLoS Med. 2017;14(3):e1002254. doi:10.1371/journal.pmed.1002254
4. Reiman EM, Arboleda-Velasquez JF, Quiroz YT, et al. Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020;11(1):667. doi:10.1038/s41467-019-14279-8
5. Badrnya S, Doherty T, Richardson C, et al. Development of a new biochip array for APOE4 classification from plasma samples using immunoassay-based methods. Clinical Chemistry and Laboratory Medicine (CCLM). 2018;56(5):796-802. doi:10.1515/cclm-2017-0618