Alzheimer’s Disease: The Role of Apolipoprotein E

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Alzheimer’s Disease: The Role of Apolipoprotein E

Alzheimer’s Disease: The Role of Apolipoprotein E

Raising awareness of Alzheimer’s Disease

Every year we celebrate Alzheimer’s Day on 21st September to help raise awareness around dementia. Dementia is the medical name attributed to a set of symptoms affecting the brain, including: difficulties with problem solving, thinking, language and memory loss. AD is the most common form of dementia accounting for 60 – 80% of cases and it is believed that half of patients with Alzheimer’s dementia (dementia due to AD) have Alzheimer’s disease 1, 2.

About Alzheimer’s Disease (AD)

AD is one of the most devastating and complex diseases characterised by:

  • Neurodegeneration resulting in memory loss 2
  • Neurofibrillary tangles composed of tau amyloid fibrils which associates with synapse loss 2
  • Accumulation of β-amyloid (Aβ) plaques 2
  • Other cognitive functions 2

Figure 1: Alzheimer’s Disease Demographic, 2019 3

It is believed that AD is expected to begin 20 years prior to symptom onset, as the small changes in the functioning of the brain are unnoticeable to the person affected. Overtime, the symptoms progress and begin to interfere with the patient’s ability to perform everyday tasks. The final stages of AD leaves the patient bed-bound, requiring 24/7 care. Ultimately, AD is fatal. Age has been identified as a risk factor for AD with 10% of people over the age of 65 affected. Moreover, AD has been recognised as a leading cause of morbidity and the sixth leading cause of mortality, but the fifth leading cause of death in over 65’s in the US .3

Physiological Significance of Apolipoprotein E

Apolipoprotein E (Apo E) is a lipoprotein composed of 299 amino acids with a molecular weight of 34kDa.  Apo E is responsible for the regulation of homeostasis through the mediation of lipid transport from and to bodily cells and tissues. Apo E comprises of three common isoforms: apo E2, apo E3 and apo E4. The apo E isoforms differ due to differences in either the 112 and 158 amino acids, whether either arginine (ARG) or cysteine (CYS) is present 4.

Apo E3 is the parent form of apo E and is responsible for the clearance of triglyceride-rich lipoproteins. Apo E3 is associated with normal lipid plasma concentrations. Apo E2 is the rarest of the apo E isoforms and differs slightly compared to the apo E3 isoform through the substitution of a single amino acid, ARG158Cys, located near the low-density lipoprotein receptor (LDLR) recognition site.

Apo E2 displays impaired binding to the receptor, prohibiting the clearance of triglyceride-rich lipoprotein remnant particles. Apo E2 is strongly associated with type-III hyperlipoproteinemia. Apo E3 also differs from apo E4, again through the substitution of a single amino acid, Cys112Arg. The main difference between apo E3 and apo E4 is that apo E4 is unaffected by the binding of the isoform to LDLR. However, apo E4 is strongly associated with dyslipidemia 5. Fig. 2 provides a visual representation of the variations in the Apo E isoforms.

Figure 2: Variations in the Apo E Isoforms 4

Apo E is expressed in numerous bodily organs with the liver presenting with the highest expression followed by the brain. Astrocytes and, to a lesser extent, microglia are the major cells responsible for the expression of apo E in the brain. In the brain, apo E, apo J and apo A-1 are predominantly expressed on distinct high-density-like lipoprotein particles. Whilst apo A-1 is the major apolipoprotein of high-density lipoproteins (HDL), in the central nervous system (CNS), apo E is the predominant apolipoprotein of HDL-like lipoproteins. HDL-like lipoproteins are the only lipoproteins present in the CNS. It is believed that the cholesterol released from apo E supports synaptogenesis 6.

Clinical Significance of Apolipoprotein E in Alzheimer’s Disease

Whilst apo E3 is the most abundant of the three isoforms, apo E4 has been known for decades to be the most significant genetic risk factor for late-onset AD. Inheriting the one copy of the apo E4 gene increases the risk of AD 2-3-fold, whilst inheriting two copies increases the risk of AD up to 12-fold 7. Whilst the underlying mechanism of apo E’s contribution to AD risk is still unclear and debatable, apo E has been identified as promoting amyloid β (Aβ) deposition and clearance as well as neurofibrillary tangles in the brain. Interestingly, Aβ-independent pathways exist for apo E in AD, which led to the unearthing of the new roles of apo E including the most recent, iron metabolism and mitochondria dysfunction 8, 9. Captivatingly, sex-related hormones may play a role in AD in apo E4 carriers as AD has been recognised to be more pronounced in women 10. Apo E4 has also been identified as impairing lipid transport, microglial responsiveness, glucose metabolism, synaptic plasticity and integrity, and cerebrovascular function and integrity. Some of these pathogeneses are independent of Aβ pathways. Furthermore, therapeutic strategies are aiming to modulate the quantity, lipidation, structural properties, Aβ interaction and receptor expression of Apo E 11.

Key Features of the Randox Apolipoprotein E Assay

Randox are one of the only manufacturers to offer the apo E assay in an automated clinical chemistry format. Utilising the immunoturbidimetric method, the Randox apo E assay is available in a liquid ready-to-use format. Not only does the Randox apo E suffer from limited interferences from bilirubin, haemoglobin, intralipid® and triglycerides for truly accurate results, it has an excellent measuring range of 1.04 – 12.3mg/dl for the comfortable detection of clinically important results. Moreover, apolipoprotein calibrator and controls are available for a complete testing package. Applications are available detailing instrument-specific settings for the convenient use of the Randox apo E assay on a wide range of clinical chemistry analysers.

Biochip Technology – Alzheimer’s Array

Utilising the Biochip Technology, Randox have developed an array to identify the risk of Alzheimer’s disease in just 3 hours with one effective test. In addition to a rapid and accurate diagnosis, this also introduces both cost and time-saving benefits. The apo E4 array is a research use only product developed for the Evidence Investigator, a semi-automated benchtop immunoassay analyser which can process up to 2376 test per hour as well as up to 44 analytes screened per biochip. The apo E4 array measures both total apo E protein levels and apo E4 protein levels directly from plasma samples as well as using a ratio, it can classify patients as negative or positive for apo E4. In turn, we can then assess their risk for the development of Alzheimer’s disease.

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World Heart Day 2021

World Heart Day 2021

World Heart DAy 2021

World Heart Day – Raising awareness of Cardiovascular Diseases

World Heart Day was established by the World Heart Federation in collaboration with the World Health Organization to raise awareness of cardiovascular diseases.

Cardiovascular disease (CVD) is the world’s number one killer, causing over 18.6 million deaths per year, according to the World Heart Federation. 85% of these deaths are due to coronary heart diseases (e.g. heart attacks) and cerebrovascular diseases (e.g. strokes) and mostly affect low-and middle-income countries.

What are cardiovascular diseases?

Cardiovascular diseases (CVDs) are a group of disorders relating to the heart and blood vessels and they include:

  • coronary heart disease – disease of the blood vessels supplying the heart muscle
  • cerebrovascular disease – disease of the blood vessels supplying the brain
  • peripheral arterial disease – disease of blood vessels supplying the arms and legs
  • rheumatic heart disease – damage to the heart muscle and heart valves from rheumatic fever, caused by streptococcal bacteria
  • congenital heart disease – malformations of heart structure existing at birth
  • deep vein thrombosis and pulmonary embolism – blood clots in the leg veins, which can dislodge and move to the heart and lungs

How can Randox help with these current global challenges

Cardiovascular disease, including heart disease, is easier to treat when detected early. Here at Randox, we utilise innovative diagnostic tests for early risk assessment capable of diagnosing disease at the earliest possible stages, because we understand that “prevention is better than cure”.

Randox Laboratories is a world leader in innovative diagnostics with 40 years’ experience and a leading provider of diagnostic reagents for the assessment of cardiovascular disease risk. Randox offer an extensive menu of cardiac biomarkers within the cardiology reagents panel including:

Risk Assessment

  • CK-MB – useful in patients with chest pain; Creatine Kinase is an enzyme produced in many different types of cells, of which high levels indicate muscle trauma or damage.
  • Myoglobin – a small protein which leaks out of muscle cells after injury, is also considered a biomarker for the detection of Myocardinal Infraction.
  • Routine lipid tests to determine the patient’s cholesterol and triglyceride levels HDL Cholesterol, LDL Cholesterol, Total Cholesterol and Triglycerides
  • Independent risk assessment tests such as sdLDL Cholesterol and Lipoprotein(a) to determine any genetic factors which may increase their risk of CVD. Please note, this is necessary even for patients who have good cholesterol levels
  • Secondary tests, such as High Sensitivity CRP, in addition to risk assessment markers and lipid evaluation – secondary tests are important in predicting future cardiac events of individuals with no previous history of CVD and those deemed healthy because of primary tests; approximately half of all heart attacks occur in patients classified as low risk. In addition, they can also be used to evaluate the risk of a recurrent cardiac event
  • Homocysteine – elevated levels of homocysteine have been linked to various disease states including CVD. Extremely high levels are found in patients with homocystinuria, of which many suffer from early arteriosclerosis.

More information

If you are a clinician or lab interested in our Cardiology & Lipids Panel, we have a wealth of resources available:

Download our Reagents Brochure 

Download our Cardiology & Lipid Testing Brochure

If you would like to get in touch with a Sales representative please email us reagents@randox.com

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Largest COVID PCR testing provider announces new nationwide network of ‘adaptive’ labs

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Tuesday 28 September 2021:  Largest COVID PCR testing provider announces new nationwide network of ‘adaptive’ labs

Randox, the UK’s largest laboratory diagnostics company, today announces its most significant expansion to date – the opening of 10 new adaptive “cube” laboratories within Great Britain. These facilities provide a rapid and cost-effective model to expand laboratory provision.   They will improve accessibility to Covid testing, facilitate wider screening services and adapt to future health and testing challenges.  Based on a modular format, sites can be operational within weeks and be redeployed if required.

The laboratories will initially be used to enhance the UK’s COVID-19 testing capacity during the winter, with each lab’s daily capacity of 12,000 tests combining to bring online an additional 120,000 COVID samples per day.  They can subsequently be re-purposed to meet the UK’s post COVID diagnostic requirements.

The opening of the new laboratories, which upon completion, will create 700 new jobs across the UK, follows £30 million of investment by Randox, bringing its total COVID-19 investment to £150 million. Two of Randox’s ten new labs are already operational outside Manchester, with two sites to the north of London opening before the end of the month. Following this, a further six labs are set to open by the end of 2021.

Commenting on the announcement Dr Peter FitzGerald, Randox Managing Director, said;

“Whilst the initial emphasis of these new laboratories will be on providing accessible, reliable and cost-effective COVID PCR tests, we of course acknowledge the positive steps being taken to ease restrictions and continue opening up our economy.

“We can draw on what we have learnt both pre and during COVID, leveraging the extensive logistics framework and IT infrastructure we have put in place, to directly address the global shortfall in laboratory testing capacity that has been exposed by the pandemic.

“The time taken to establish the required diagnostic infrastructure in the early stages of the pandemic adversely impacted the international response, but with such an adaptable capability, the UK can, as and when needed, respond rapidly to ever-increasing diagnostic demand.”

The new adaptive laboratories from Randox will ensure the provision of travel testing for those who still require them, and can also support any surge testing for the UK’s National COVID Testing Programme; Randox has processed and reported over 18 million COVID PCR samples to date.  Randox also facilitate Covid-19 lateral flow testing.

Having used its 40 years’ experience in diagnostics to focus the business towards COVID testing and support the fight against the virus, Randox, established in 1982, will subsequently use its new lab sites to service a wider UK system of walk-in clinics which can offer whole-body diagnostic screening programmes.

Dr FitzGerald continued;

“The legacy of COVID is that people increasingly understand and appreciate the importance of diagnostics and testing across our society, and as such we anticipate a real appetite from people to take greater interest in their health.

“We will continue COVID testing where necessary but will harness this high-volume testing capacity to pivot back to our core business offering of clinical health tests. The investment we have made in COVID lab facilities will allow us to build a national testing network that will facilitate a shift towards a new era of preventative healthcare, in which ill-health and disease are detected at the earliest possible opportunity, potentially even before symptoms appear.

“Our new adaptive laboratories will fundamentally be a game-changer for the UK’s future diagnostics requirements – improving patient outcomes and reducing the burden on healthcare services.”

 

For further information on Covid testing services please contact the Randox Covid Customer Support team on covidcustomersupport@randox.com  or +44 (0) 28 9434 3005.

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SARS-CoV-2 Vascular & Multi-System Dysfunction Whitepaper

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30 June 2021

SARS-CoV-2 Vascular & Multi-System Dysfunction Whitepaper Download

COVID-19, the disease caused by SARS-CoV-2, is an infectious disease caused by a newly discovered coronavirus. While many of whom become infected by the disease will experience mild to moderate cold or flu-like symptoms, those with health complications – such as autoimmune diseases, asthma, heart disease and diabetes – are at risk of developing serious illness and adverse outcomes.

As of September 2021, over 228 million COVID-19 cases have been confirmed worldwide, with an estimated one in six patients experiencing complications which could be life threatening, with over £116 billion spent by the UK government alone on measures to combat the disease. This drastic spending has been mirrored across the globe, with the significant economic burden expected to be suffered for generations to come.

The whitepaper provides a brief overview of the COVID-19 pandemic, before discussing vascular abnormalities and associated complications brought on by the virus, such as multi-system disfunction, acute respiratory disease syndrome (ARDS) and hepatic, renal & cardiovascular function.

 

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Why does Randox sponsor Equine Sports events?

Why does Randox sponsor Equine Sports?

1 September 2021: Why does Randox sponsor Equine Sports?

Some may be wondering, why is a healthcare company so invested in the equine industry? Why would they sponsor the world’s most famous steeplechase – The Randox Grand National?

It’s a labour of love… Peter FitzGerald’s fond attachment to the equestrian world, together with 40 years’ experience in the in vitro diagnostics industry, was the perfect match.

Clinical diagnostics is at the heart of Randox and our experience and expertise has paved the way for the development of innovative and accurate diagnostic products for Equine Health.

You could say ‘it runs in our blood.’

With 70% of all medical decisions based on the analysis of blood, Randox are set to release the VeraSTAT-V, a stable-side Equine Serum Amyloid A test device designed to detect levels of inflammation in horse blood in a matter of minutes.

The ability to quickly detect and monitor your horse’s health, at the stable side, brings huge benefits to both horse and owner. Early detection of inflammatory states means treatment plans can start sooner, recovery periods are shorter, and the horse can return to work healthy much earlier.

When performance is key, monitoring inflammation is vital.

Whether it’s detecting inflammation related to joint injury, or screening for infection before or after transport, competition or surgery, the VeraSTAT-V is a valuable means to monitor Equine Health.

At Randox, we have enjoyed a long-standing partnership with the Jockey Club and will continue to deliver innovative diagnostics solutions to the Equine Industry for the years ahead.

Interested in finding out more? 

For all Equine SAA and/or Veterinary related inquiries, please email marketing@randox.com or visit www.randox.com/veraSTAT-V for more information.

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Collinson and Randox partner to launch rapid airport PCR for travel testing

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Tuesday 07 September 2021: Collinson and Randox partner to launch rapid airport PCR for travel testing

Rapid PCR technology means passengers can receive results in under three hours on the day of departure

Collinson has today announced it has partnered with biotech company, Randox, to offer rapid PCR testing. The ground-breaking new testing offering, which is already available at Collinson’s new park and test facility near Heathrow Airport, uses advanced on-site Randox technology to process RT-PCR – the gold standard of Covid-19 virus testing – in under three hours. It means passengers who require a negative PCR result to fly can, for the first time, book to take the test on their day of departure and have their result in time for check-in, rather than needing to arrange for a test days in advance.

Today’s announcement from Collinson and Randox will make the PCR testing process far more seamless for passengers, enabling them to book to take their test as part of the journey to the airport. In the next few weeks, the new technology will also be launched at Collinson’s drive-through facility near Gatwick.

With testing numbers skyrocketing as more people look to get abroad in line with UK restrictions lifting, Collinson is launching the rapid Randox testing as another option to help meet increased demand. Collinson has been a front-runner in travel testing solutions across the UK since it launched its first facility last summer and led the way in getting rapid genetic LAMP testing technology accredited for ‘Day 5’ testing.

Today’s partnership with Randox combines the medical and biological expertise and experience both companies have gained in travel testing over the past year. The joining of the two British companies and this new, rapid PCR technology means cheaper, faster and more reliable same day testing for anyone departing from the UK, which is sure to be a boost to both the country’s travel industry recovery as well the UK’s trade in general.

This new offering means that passengers with bookings can take a rapid PCR test the day they travel. As processing is handled on site rather than couriered to a lab; it is quicker while being just as reliable. While awaiting their test result, passengers can proceed to the airport terminal and enjoy a coffee, before going to check-in.

“We’ve come such a long way in travel testing since we first started speaking to the UK Government about our solutions last summer,” said Dr. Simon Worrell, Global Medical Director, Collinson. “The new, rapid PCR tests we’re announcing with Randox today really are the most sophisticated tests on the market. No longer do travellers need to take a PCR test three days before travel, and so risk contracting the virus in the interim. They’re a complete game-changer for anyone looking to travel at this time, making the testing process as seamless as possible for passengers as they can conveniently take their test on their way to the airport, rather than needing to find somewhere to be tested days in advance.”

“We are pleased to have partnered with Collinson, which has been leading the way in travel testing and recovery since last summer,” said David Ferguson, Managing Director, Randox. “We at Randox have been on the front line in the fight against COVID-19 since its outbreak last year and both of our companies know how important testing is to travel recovery. We’re thrilled to come together to pioneer rapid PCR testing – once more doing our bit to get the travel industry back on its feet and the world moving once more.  This partnership allows Randox to further advance its service delivery in the fight against Covid-19 and offer ground-breaking medical diagnostics to ensure rapid and effective PCR testing. Travel during the pandemic has undoubtedly been challenging, but with this partnership I am confident that travel will now be far more accessible and achievable to those who use this service.”

The cost of a rapid PCR test is £95. To book visit collinsongroup.com

As a UKAS-approved testing provider, in addition to RT-PCR tests, Collinson will continue to offer a range of COVID-19 testing solutions for pre-departure and post-arrival at its facilities nationwide. Destination entry requirements differ depending on whether you are fully vaccinated or not. Travellers should check the entry requirements of their intended destination country using the GOV.UK foreign travel advice pages to be confident in their requirements.

Randox, with almost 40 years of international diagnostics experience, has been at the forefront of COVID-19 testing since the outset of the pandemic. With proven testing capability and well-established logistics and customer support services, Randox are strongly placed to allow international travellers to travel with confidence.

 

For further information on Covid testing services please contact the Randox Covid Customer Support team on +44 (0) 28 9434 3005.

 

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