Alzheimer’s Disease, ApoE & Risk Detection
Alzheimer’s Disease, ApoE & Risk Detection
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 aggregates1,2. 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
- 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
- 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
- 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
- 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
- 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
The medical techniques keeping Team GB healthy during the Olympic Games
There was a time when you could count the number of British gold medallists on the fingers of one hand. Back in the 1960s and 1970s, winning an Olympics event made you a household name overnight.
Anne Packer, Lynn Davies, Mary Peters, David Hemery, Anita Lonsbrough, – to name a few of the few – were feted across the land to pulling off the seemingly impossible – beating the world, usually in track and field or the swimming pool.
But all that has changed.
London 2012 (29 gold medals); Rio de Janeiro 2016 (27 gold); Tokyo 2020 but actually in 2021 (22 gold).
Time was when most Olympics hopefuls were fanatical amateurs, prepared to turn out on some bleak and chilly track, strip down to their shorts and practise their sport in front of an equally dedicated but minority audience.
Not any more. The British medals haul, however you measure it, is also top of the tree on an international basis. A country of fewer than 70 million people typically comes in the top three or four on the planet behind only the likes of such giants such as the USA and China. We even beat the Australians – on a regular basis.
This has not happened by accident.
Obviously, a huge amount of credit must go to the athletes themselves and their coaches. Their talent and dedication will be fully on display in Paris this week when the Games return to France for the first time in exactly 100 years.
But there is much more to it than that. Team GB has revolutionised British Olympics in recent years. The team numbers more than 300 and for only the second time in our history, there will be more women (172) than male (155) competitors.
Professional coaches, physios, nutritionists, and mind game experts will abound.
The Greatest Show on Earth will dominate our TV screens, social media, press and national conversation for a fortnight (and more).
These are some of the reasons why Randox, Europe’s biggest diagnostic company, is sponsoring Team GB. We love supporting the athletes behind mega sporting events (The Grand National, for instance) and it does not come any more mega than Paris 2024.
We were there the last time – Tokyo 2020 – but in challenging circumstances. Tokyo 2020 actually took place in 2021, postponed for a year because of the Covid pandemic.The glittering contests were performed in front of empty stadiums and sports halls after the Olympic authorities, understandably anxious to avert a super-spreader car crash, prohibited spectators.
Founded in 1982, Randox conducted more than 27 million Covid tests in the UK and offered support to Team GB three years ago for a very specific and vital purpose – to help stop the spread of Covid among the athletes and their support teams. It worked. Despite the fears of the Olympic authorities, the plethora of measures taken to safeguard contestants, meant that only one athlete fell sick and was unable to compete.
Not so this time. 15 million people, two million from abroad, are expected to swamp the French capital over late July and early August.
Our Vivalytic diagnostic machine, used in Tokyo to test all our athletes for Covid, will be in action again. But this time, we will be casting the net far wider, checking for a range of respiratory infections that can lay contestants low.
Our aim, along with the teams of experts assisting our athletes is simple – to ensure that Team GB is in peak physical and mental condition as they get to the starting line.
We have also been working closely with our brand ambassadors to ensure that they are perfectly placed to perform to their utmost in Paris. All of them have undertaken our Everyman and Everywoman diagnostic health testing packages at one of our health clinics, to measure their condition as they prepare for Paris.
As one star, Duncan Scott, our most decorated Olympic swimmer, put it: “If it makes one per cent difference, it’s 100 per cent worth it.
“It excited me that it was essentially a head-to-toe MOT and there’s areas I’ve never really had much data, on but also last year I had an IgE (antibody) deficiency impacting my immune system which made training so inconsistent as some days I felt sluggish.
“This year has been much more consistent after picking up on it which makes me wish I had something like this, as if I did this last year or 24 months ago, it’d have been ideal going in unknown and then picking up on it as a risk rather than me getting frustrated and being ill.”
Top sprinter Daryll Neita, a multiple medal winner, took the Everywoman test, “the most in-depth testing I’ve ever had.”
Her verdict points to the confidence boost of knowing you are in peak condition physically: “Although I’ve not had any recent health concerns, it’s amazing that the Everywoman test discovers things that could help my performance.
“Whether it’s how I recover or deficiencies, but also our sport is about marginal gains, centimetres, millimetres, the finest of margins and through tests like this, it lets you stay on-top of your health, helping you achieve optimal performance or even a mental boost that you’re healthy.”
Team GB’s Chief Medical Officer Niall Elliott, said that Randox was helping in three critical areas of health testing for athletes – iron metabolism, vitamin D levels – critical to the immune system and muscle power – and glucose or energy levels. “It is a fascinating journey, the testing we can do.”
This must be the best prepared – and the most safeguarded – Team GB ever to leave our shores.
As devotees of the wonderful film, Chariots of Fire, will know, they have much to live up to. Back in the 1924 Paris Olympics, Harold Abrahams in the 100 metres and Eric Liddell in the 400 metres both emerged triumphant. On top of their legendary feats, Britain secured seven more gold medals.
We can only hope and pray that our champions, bolstered by the latest in sports science, can achieve even greater heights.
Words by Dr. Peter FitzGerald, Sunday Express https://www.express.co.uk/news/politics/1925873/medical-techniques-keeping-team-gb
