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Scientists Close in on Elusive Goal of Adapting Nanopore Technology for Protein Sequencing

Technology could enable medical laboratories to deploy inexpensive protein sequencing with a handheld device at point of care and remote locations

Clinical laboratories engaged in protein testing will be interested in several recent studies that suggest scientists may be close to adapting nanopore-sensing technology for use in protein identification and sequencing. The new proteomics techniques could lead to new handheld devices capable of genetic sequencing of proteins at low cost and with a high degree of sensitivity, in contrast to current approaches based on mass spectrometry.

But there are challenges to overcome, not the least of which is getting the proteins to cooperate. Compact devices based on nanopore technology already exist that can sequence DNA and RNA. But “there are lots of challenges with proteins” that have made it difficult to adapt the technology, Aleksei Aksimentiev, PhD, Professor of Biological Physics at the University of Illinois at Urbana-Champaign, told ASBMB Today, a publication of the American Society for Biochemistry and Molecular Biology. “In particular, they’re not uniformly charged; they’re not linear, most of the time they’re folded; and there are 20 amino acids, plus a zoo of post-translational modifications,” he added.

The ASBMB story notes that nanopore technology depends on differences in charges on either side of the membrane to force DNA or RNA through the hole. This is one reason why proteins pose such a challenge.

Giovanni Maglia, PhD, a Full Professor at the University of Groningen in the Netherlands and researcher into the fundamental properties of membrane proteins and their applications in nanobiotechnology, says he has developed a technique that overcomes these challenges.

“Think of a cell as a miniature city, with proteins as its inhabitants. Each protein-resident has a unique identity, its own characteristics, and function. If there was a database cataloging the fingerprints, job profiles, and talents of the city’s inhabitants, such a database would undoubtedly be invaluable!” said Behzad Mehrafrooz, PhD (above), Graduate Research Assistant at University of Illinois at Urbana-Champaign in an article he penned for the university website. This research should be of interest to the many clinical laboratories that do protein testing. (Photo copyright: University of Illinois.)

How the Maglia Process Works

In a Groningen University news story, Maglia said protein is “like cooked spaghetti. These long strands want to be disorganized. They do not want to be pushed through this tiny hole.”

His technique, developed in collaboration with researchers at the University of Rome Tor Vergata, uses electrically charged ions to drag the protein through the hole.

“We didn’t know whether the flow would be strong enough,” Maglia stated in the news story. “Furthermore, these ions want to move both ways, but by attaching a lot of charge on the nanopore itself, we were able to make it directional.”

The researchers tested the technology on what Maglia described as a “difficult protein” with many negative charges that would tend to make it resistant to flow.

“Previously, only easy-to-thread proteins were analyzed,” he said in the news story. “But we gave ourselves one of the most difficult proteins as a test. And it worked!”

Maglia now says that he intends to commercialize the technology through a new startup called Portal Biotech.

The Groningen University scientists published their findings in the journal Nature Biotechnology, titled “Translocation of Linearized Full-Length Proteins through an Engineered Nanopore under Opposing Electrophoretic Force.”

Detecting Post-Translational Modifications in the UK

In another recent study, researchers at the University of Oxford reported that they have adapted nanopore technology to detect post-translational modifications (PTMs) in protein chains. The term refers to changes made to proteins after they have been transcribed from DNA, explained an Oxford news story.

“The ability to pinpoint and identify post-translational modifications and other protein variations at the single-molecule level holds immense promise for advancing our understanding of cellular functions and molecular interactions,” said contributing author Hagan Bayley, PhD, Professor of Chemical Biology at University of Oxford, in the news story. “It may also open new avenues for personalized medicine, diagnostics, and therapeutic interventions.”

Bayley is the founder of Oxford Nanopore Technologies, a genetic sequencing company in the UK that develops and markets nanopore sequencing products.

The news story notes that the new technique could be integrated into existing nanopore sequencing devices. “This could facilitate point-of-care diagnostics, enabling the personalized detection of specific protein variants associated with diseases including cancer and neurodegenerative disorders,” the story states.

The Oxford researchers published their study’s findings in the journal Nature Nanotechnology titled, “Enzyme-less Nanopore Detection of Post-Translational Modifications within Long Polypeptides.”

Promise of Nanopore Protein Sequencing Technology

In another recent study, researchers at the University of Washington reported that they have developed their own method for protein sequencing with nanopore technology.

“We hacked the [Oxford Nanopore] sequencer to read amino acids and PTMs along protein strands,” wrote Keisuke Motone, PhD, one of the study authors in a post on X (formerly Twitter) following the study’s publication on the preprint server bioRxiv titled, “Multi-Pass, Single-Molecule Nanopore Reading of Long Protein Strands with Single-Amino Acid Sensitivity.”

“This opens up the possibility for barcode sequencing at the protein level for highly multiplexed assays, PTM monitoring, and protein identification!” Motone wrote.

In a commentary they penned for Nature Methods titled, “Not If But When Nanopore Protein Sequencing Meets Single-Cell Proteomics,” Motone and colleague Jeff Nivala, PhD, Principal Investigator at University of Washington, pointed to the promise of the technology.

Single-cell proteomics, enabled by nanopore protein sequencing technology, “could provide higher sensitivity and wider throughput, digital quantification, and novel data modalities compared to the current gold standard of protein MS [mass spectrometry],” they wrote. “The accessibility of these tools to a broader range of researchers and clinicians is also expected to increase with simpler instrumentation, less expertise needed, and lower costs.”

There are approximately 20,000 human genes. However, there are many more proteins. Thus, there is strong interest in understanding the human proteome and the role it plays in health and disease.

Technology that makes protein testing faster, more accurate, and less costly—especially with a handheld analyzer—would be a boon to the study of proteomics. And it would give clinical laboratories new diagnostic tools and bring some of that testing to point-of-care settings like doctor’s offices.

—Stephen Beale

Related Information:

Nanopores as the Missing Link to Next Generation Protein Sequencing

Nanopore Technology Achieves Breakthrough in Protein Variant Detection

The Scramble for Protein Nanopore Sequencing

The Emerging Landscape of Single-Molecule Protein Sequencing Technologies

ASU Researcher Advances the Science of Protein Sequencing with NIH Innovator Award          

The Missing Link to Make Easy Protein Sequencing Possible?

Engineered Nanopore Translocates Full Length Proteins

Not If But When Nanopore Protein Sequencing Meets Single-Cell Proteomics

Enzyme-Less Nanopore Detection of Post-Translational Modifications within Long Polypeptides

Unidirectional Single-File Transport of Full-Length Proteins through a Nanopore

Translocation of Linearized Full-Length Proteins through an Engineered Nanopore under Opposing Electrophoretic Force

Interpreting and Modeling Nanopore Ionic Current Signals During Unfoldase-Mediated Translocation of Single Protein Molecules

Multi-Pass, Single-Molecule Nanopore Reading of Long Protein Strands with Single-Amino Acid Sensitivity

New Zealand Clinical Laboratories to Undergo Health and Safety Checks after Workers Contract Typhoid, Others Exposed to Chemicals

This comes on top of months of strikes by NZ medical laboratory workers seeking fair pay and safe working conditions

Te Whatu Ora (aka, Health New Zealand, the country’s publicly funded healthcare system) recently ordered health and safety checks at multiple clinical laboratories in 18 districts across the country. This action is the result of safety issues detected after procedural discrepancies were discovered in separate labs.

According to Radio New Zealand(RNZ), Health New Zealand found “significant risks” at some medical laboratories and that “staff at one in Auckland were exposed to toxic fumes, at others two [people] caught typhoid, and delays jeopardized patients’ care.”

“Two lab workers were hospitalized this year after having caught typhoid from samples, one at a private lab in Auckland, and a second at Canterbury Health Laboratories, CHL,” RNZ reported.

A Health New Zealand internal document states there will need to be a “comprehensive” fix to deal with risks present in the island nation’s medical laboratory industry. The assessment states that the organization needs “a more detailed picture of the occupational health and health and safety risks present in our laboratories,” RNZ reported.

“The overall state of the laboratories and the practices they have in place pose an inherited risk from the former DHBs [district health boards] and will likely need a comprehensive approach to addressing significant and/or ongoing risks,” Health New Zealand said in the internal document. “There is growing demand on our laboratories in terms of the volume of the work, which can put pressure on processes, and work is often undertaken in facilities that, over time, may have become not fit for purpose.”

This story as an example of how clinical laboratory staff can be exposed to disease and toxic chemicals when procedures are not diligently followed. It is a reminder to all lab managers that diligence in following protective protocols is imperative.

“Te Whatu Ora is committed to identifying, tracking and mitigating all potential risks and issues within our service until they are fully resolved and no longer identifiable as an issue/risk,” Rachel Haggerty (above), Director, Strategy, Planning and Purchasing, Hospital and Specialist Services, for Health New Zealand told NZ Doctor. Clinical laboratory workers in New Zealand have been striking for fair pay and safe working environments for months. Now, they risk becoming infected by deadly pathogens and chemicals as well. (Photo copyright: NZ Doctor.)

Lab Worker Strikes and Staff Shortages

Community Anatomic Pathology Services in Auckland lost its histology accreditation last year because it was discovered that lab workers were exposed to toxic chemical levels at the facility. In addition, patients were forced to wait weeks for test results from that lab. 

The laboratory was also penalized back in 2017 for how substances were handled when formaldehyde levels in excess of the recommended limits were detected. 

Bryan Raill, a medical scientist at the Counties Manukau District Health Board, said the laboratory workers union in New Zealand believes staff shortages and lab conditions are contributing to the lab woes. Raill is also president of the medical laboratory workers division of APEX, a specialist union representing more than 4,000 allied, scientific, and technical health professionals throughout New Zealand.

“It’s not only your physical environment, being safe there, but you have to be safe in terms of what you do,” Raill told RNZ.

Raill said the two typhoid infections were a red flag and that Te Whatu Ora needs to do more.

“They’re stepping out of the inertia they’ve been bound, so this is a good thing, but it needs to be a wider thing,” he said.

The New Zealand Institute of Medical Laboratory Science (NZIMLS) warned the government months ago that lab technicians were under unsustainable pressure.

“They should look at the other health and safety aspect of the workload and the work environment that staff are working under,” Raill explained in an iHeart podcast. “The person who caught typhoid in Christchurch spent four days in ICU, and there had been a workplace exposure to another pathogen two years earlier and the recommendations that came out of that hadn’t been followed. For example, [the lab workers] were not vaccinated against typhoid.”

IT Implementation Delays also to Blame

Along with strikes and staff shortages, clinical laboratories in New Zealand are also dealing with information technology (IT) issues. Technical problems have delayed some needed lab upgrades by more than a year. 

In addition, “The impacts of new test, surgeries, and medicines/treatments on pathology services have also historically not been understood well nor accounted for and we are considering a number of options, as outlined in the risk register, to manage this,” said Rachel Haggerty, Director, Strategy, Planning and Purchasing, Hospital and Specialist Services, for Te Whatu Ora.

Future efforts will deal with training of lab personnel and focus on ventilation and hazardous substance management. 

Dark Daily has reported extensively on the ongoing problems within New Zealand clinical laboratory industry.

In “Pathology Lab Shortages in New Zealand Are One Cause in Long Delays in Melanoma Diagnoses,” we reported how pathology shortages were causing some patients to wait for more than a month for a melanoma diagnosis. And that the situation is putting cancer patients’ lives at risk.

And in “Medical Laboratory Workers Again on Strike at Large Clinical Laboratory Company Locations around New Zealand,” we covered ongoing strikes by medical technicians, phlebotomists, and clinical laboratory scientists in New Zealand and how their complaints mirror similar complaints by healthcare and clinical laboratory workers in the US.

Clinical laboratory personnel can be exposed to dangerous diseases and toxic chemicals when procedures are not diligently followed. This latest situation in New Zealand serves as a reminder that following protective protocols is imperative in labs worldwide to protect workers and patients.

—JP Schlingman

Related Information:

Te Whatu Ora Finds ‘Significant’ Risks at Labs, Workers Catch Typhoid from Samples, Exposed to Fumes

How to Fix the NZ Laboratory Fiasco

Private Healthcare Pushing Auckland Labs to the Brink

Bryan Raill: Apex Union President Urges Te Whatu Ora to Thoroughly Assess Risk in New Zealand Laboratories

Pathology Lab Shortages in New Zealand Are One Cause in Long Delays in Melanoma Diagnoses

Medical Laboratory Workers Again on Strike at Large Clinical Laboratory Company Locations around New Zealand

Four Thousand New Zealand Medical Laboratory Scientists and Technicians Threatened to Strike over Low Pay and Poor Working Conditions

BMJ Oncology Study Shows 79% Increase in Cancer among People under 50 Years of Age

Findings suggest new medical guidelines may be needed to determine when to perform clinical laboratory cancer screenings on people under 50

From 1990-2019, new diagnoses of early-onset cancer in individuals under 50 years of age increased by 79%, according to a British Medical Journal (BMJ) news release describing research published last year in BMJ Oncology. The question for anatomic pathology laboratories to consider is, why are more people under 50 being diagnosed with cancer than in earlier years? And do medical guidelines need to be changed to allow more cancer screening for individuals under 50-years old?

This new revelation challenges previously held beliefs about the number of younger adults under 50 experiencing early-onset cancer. Patients can sometimes miss symptoms by attributing them to a more benign condition.

“While cancer tends to be more common in older people, the evidence suggests that cases among the under 50s have been rising in many parts of the world since the 1990s. But most of these studies have focused on regional and national differences; and few have looked at the issue from a global perspective or the risk factors for younger adults, say the researchers. In a bid to plug these knowledge gaps, they drew on data from the Global Burden of Disease 2019 Study for 29 cancers in 204 countries and regions,” the BMJ news release states.

According to the news release, “Breast cancer accounted for the highest number of ‘early-onset’ cases in this age group in 2019. But cancers of the windpipe (nasopharynx) and prostate have risen the fastest since 1990, the analysis reveals. Cancers exacting the heaviest death toll and compromising health the most among younger adults in 2019 were those of the breast, windpipe, lung, bowel, and stomach.”

Although these statistics are being seen worldwide, the highest rates are in North America, Australasia, and Western Europe. However, high death rates due to cancer are also being seen in Eastern Europe, Central Asia, and Oceania. Economic disparities in the latter geographical regions may account for both fewer diagnoses and higher death rates.

“And in low to middle income countries, early onset cancer had a much greater impact on women than on men, in terms of both deaths and subsequent poor health,” the BMJ news release noted.

In an editorial they published in BMJ Oncology on the study findings, Ashleigh Hamilton, PhD (left), Academic Clinical Lecturer, and Helen Coleman, PhD (right), Professor, School of Medicine, Dentistry and Biomedical Sciences, both at the Center for Public Health at Queen’s University Belfast in the UK wrote, “The epidemiological landscape of cancer incidence is changing. … Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.” Anatomic pathology laboratories will play an important role in diagnosing and treating younger cancer patients. (Photo copyrights: Queen’s University Belfast.)

What Caused the Increase?

“It’s such an important question, and it points to the need for more research in all kinds of domains—in population science, behavioral health, public health, and basic science as well,” said medical oncologist Veda Giri, MD, Professor of Internal Medicine, Yale School of Medicine, in a news release. Giri directs the Yale Cancer Center Early-Onset Cancer Program at Smilow Cancer Hospital.

Although experts are still trying to determine exactly where these cases are coming from, signs point to both genetic and lifestyle factors, the BMJ news releases noted. Tobacco and alcohol use, diets high in cholesterol and sodium, and physical inactivity are all lifestyle risk factors. Experts recommend a healthy diet and exercise routine with minimal alcohol consumption.

As for family history? “We’re beginning to recognize that family history is very important,” says Jeremy Kortmansky, MD, also a Yale Medicine medical oncologist.

According to CNN Health, these rates of early-onset cancer are more common in female patients, with rates going up an average of 0.67% each year.

“For young women who have a significant family history of cancer in the family, we are starting to refer them to a high-risk clinic—even if the cancer in their family is not breast cancer,” Kortmansky noted.

Doctors advise patients to implement healthy habits into their lives, not ignore symptoms, advocate for themselves, and be aware of their family history. Cancer patients may be prescribed cancer treatments at a much earlier age. Medical guidelines for patients may continue to shift and change. And oncologists may be incorporating alternative therapies to help younger patients deal with the shock of their diagnosis.

Will Cancer Rates Continue to Rise?

“Based on the observed trends for the past three decades, the researchers estimate that the global number of new early-onset cancer cases and associated deaths will rise by a further 31% and 21% respectively in 2030, with those in their 40s the most at risk,” the BMJ news release noted.

In an editorial they penned for BMJ Oncology on the findings of the cancer study titled, “Shifting Tides: The Rising Tide of Early-Onset Cancers Demands Attention,” Ashleigh Hamilton, PhD, Academic Clinical Lecturer, and Helen Coleman, PhD, Professor, School of Medicine, Dentistry and Biomedical Sciences, both at the Center for Public Health at Queen’s University Belfast in the UK wrote, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored. It is crucial that we better understand the underlying reasons for the increase in early-onset cancers, in order to inform prevention strategies.”

Clinical laboratories should be aware of these findings and the changing landscape of cancer screenings, as they will play a key role in diagnoses. Younger patients may be advocating for cancer screenings and doctors may be ordering them depending on the patient’s symptoms and family history. Anatomic pathology professionals should expect new guidelines when it comes to cancer diagnostics and treatment.

—Ashley Croce

Related Information:

Global Surge in Cancers among the Under 50s over Past Three Decades

Shifting Tides: The Rising Tide of Early-Onset Cancers Demands Attention

Global Trends in Incidence, Death, Burden and Risk Factors of Early-Onset Cancer from 1990 to 2019

Cancer Diagnosis Rates are Going up in Younger Adults, Study Finds, Driven Largely By Rises in Women and People in Their 30s

Early Onset Cancer Cases Rise 80% in Past Three Decades, BMJ Survey Finds

Cancer in Younger People Is on the Rise: Knowing Your Family History Can Help

Study Points to Big Surge in Under-50 Cancer Cases

Researchers See Surge in Number of People under 50 Diagnosed with Cancer

University of Gothenburg Study Findings Affirm Accuracy of Clinical Laboratory Blood Test to Diagnose Alzheimer’s Disease

Already-existing clinical laboratory blood test may be new standard for detecting Alzheimer’s biomarkers

In Sweden, an independent study of an existing blood test for Alzheimer’s disease—called ALZpath—determined that this diagnostic assay appears to be “just as good as, if not surpass, lumbar punctures and expensive brain scans at detecting signs of Alzheimer’s in the brain,” according to a report published by The Guardian.

Alzheimer’s disease is one of the worst forms of dementia and it affects more than six million people annually according to the Alzheimer’s Association. Clinical laboratory testing to diagnose the illness traditionally involves painful, invasive spinal taps and brain scans. For that reason, researchers from the University of Gothenburg in Sweden wanted to evaluate the performance of the ALZpath test when compared to these other diagnostic procedures.

Motivated to seek a less costly, less painful, Alzheimer’s biomarker for clinical laboratory testing, neuroscientist Nicholas Ashton, PhD, Assistant Professor of Neurochemistry at the University of Gothenburg, led a team of scientists that looked at other common biomarkers used to identify changes in the brain of Alzheimer’s patients. That led them to tau protein-based blood tests and specifically to the ALZpath blood test for Alzheimer’s disease developed by ALZpath, Inc., of Carlsbad, Calif.

The researchers published their findings in the journal JAMA Neurology titled, “Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.”

In their JAMA article, they wrote, “the pTau217 immunoassay showed similar accuracies to cerebrospinal fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies.”

In an earlier article published in medRxiv, Ashton et al wrote, “Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer’s disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited.”

Thus, the discovery of an existing pTau217 assay (ALZpath) that is accessible and affordable is a boon to Alzheimer’s patients and to the doctors who treat them.

“The ALZpath pTau217 assay showed high diagnostic accuracy in identifying elevated amyloid (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau (AUC, 0.93-0.97; 95%CI 0.84-0.99) in the brain across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and equivalent to CSF [cerebrospinal fluid] biomarkers,” an ALZpath press release noted.

“This is an instrumental finding in blood-based biomarkers for Alzheimer’s, paving the way for the clinical use of the ALZpath pTau217 assay,” stated Henrik Zetterberg, MD, PhD (above), Professor of Neurochemistry at the University of Gothenburg and co-author of the study. “This robust assay is already used in multiple labs around the globe.” Clinical laboratories may soon be receiving doctors’ orders for pTau217 blood tests for Alzheimer’s patients. (Photo copyright: University of Gothenburg.)

Study Details

Ashton’s team conducted a cohort study that “examined data from three single-center observational cohorts.” The cohorts included:

“Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023,” the researchers wrote. 

These trials from the US, Canada, and Spain featured 786 participants and featured “either a lumbar puncture or an amyloid PET scan to identify signs of amyloid and tau proteins—hallmarks of Alzheimer’s disease,” The Guardian reported, adding that results of the University of Gothenburg’s study showed that the ALZpath pTau217 blood test “was superior to brain atrophy assessments, in identifying signs of Alzheimer’s.”

“80% of individuals could be definitively diagnosed on a blood test without any other investigation,” Ashton told The Guardian.

Diagnosis Needed to Receive Alzheimer’s Disease Treatments

“If you’re going to receive [the new drugs], you need to prove that you have amyloid in the brain,” Ashton told The Guardian. “It’s just impossible to do spinal taps and brain scans on everyone that would need it worldwide. So, this is where the blood test [has] a huge potential.”

Even countries where such drugs were not yet available (like the UK) would benefit, Ashton said, because the test, “Could potentially say that this is not Alzheimer’s disease and it could be another type of dementia, which would help to direct the patient’s management and treatment routine.”

However, Ashton himself noted the limitations of the new findings—specifically that there is no success shown yet in Alzheimer’s drugs being taken by symptom-free individuals.

“If you do have amyloid in the brain at 50 years of age, the blood test will be positive,” he said. “But what we recommend, and what the guidelines recommend with these blood tests, is that these are to help clinicians—so someone must have had some objective concern that they have Alzheimer’s disease, or [that] their memory is declining,” he told The Guardian.

Experts on the Study Findings

“Blood tests could be used to screen everyone over 50-years old every few years, in much the same way as they are now screened for high cholesterol,” David Curtis, MD, PhD, Honorary Professor in the Genetics, Evolution and Environment department at University College London, told The Guardian.

“Results from these tests could be clear enough to not require further follow-up investigations for some people living with Alzheimer’s disease, which could speed up the diagnosis pathway significantly in future,” Richard Oakley, PhD, Associate Director of Research and Innovation at the Alzheimer’s Society, UK, told The Guardian.

Though Oakley found the findings promising, he pointed out what should come next. “We still need to see more research across different communities to understand how effective these blood tests are across everyone who lives with Alzheimer’s disease,” he said.

“Expanding access to this highly accurate Alzheimer’s disease biomarker is crucial for wider evaluation and implementation of AD blood tests,” the researchers wrote in JAMA Neurology.

“ALZpath makers are in discussions with labs in the UK to launch it for clinical use this year, and one of the co-authors, Henrik Zetterberg, MD, PhD, Professor of Neurochemistry at the University of Gothenburg, is making the assay available for research use as part of the ‘biomarker factory’ at UCL,” The Guardian reported.

In the US, to be prescribed any of the available Alzheimer’s medications, a doctor must diagnose that the patient has amyloid in the brain. A pTau217 diagnostic blood test could be used to make such a diagnosis. Currently, however, the test is only available “for research studies through select partner labs,” Time reported.

“But later this month, doctors in the US will be able to order the test for use with patients. (Some laboratory-developed tests performed by certain certified labs don’t require clearance from the US Food and Drug Administration.),” Time added.

It may be that the University of Gothenburg study will encourage Alzheimer’s doctors in the UK and around the world to consider ordering pTau217 diagnostic blood tests from clinical laboratories, rather than prescribing spinal taps and brains scans for their Alzheimer’s patients.

—Kristin Althea O’Connor

Related Information:

New Study Published in JAMA Neurology Affirms High Diagnostic Accuracy of ALZpath’s pTau217 Test in Identifying Amyloid and Tau in the Brain

Blood Test Could Revolutionize Diagnosis of Alzheimer’s, Experts Say

Simple Blood Tests for Dementia to Be Trialed in NHS

A Blood Test for Alzheimer’s Disease Is Almost Here

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

Alzheimer’s Disease Facts and Figures

Scientists Develop Blood Test for Alzheimer’s Disease

University of California San Francisco Study Finds Both High and Low Levels of High-Density Lipoprotein Cholesterol Associated with Increased Dementia Risk

If validated, study findings may result in new biomarkers for clinical laboratory cholesterol tests and for diagnosing dementia

Researchers continue to find new associations between biomarkers commonly tested by clinical laboratories and certain health conditions and diseases. One recent example comes from research conducted by the University of California San Francisco. The UCSF study connected cholesterol biomarkers generally used for managing cardiovascular disease with an increased risk for dementia as well.

The researchers found that both high and low levels of high-density lipoprotein (HDL)—often referred to as “good” cholesterol—was associated with dementia in older adults, according to a news release from the American Academy of Neurology (AAN).

UCSF’s large, longitudinal study incorporated data from 184,367 people in the Kaiser Permanente Northern California health plan. How the findings may alter cholesterol biomarker use in future diagnostics has not been determined.

The researchers published their findings in the journal Neurology titled, “Low- and High-Density Lipoprotein Cholesterol and Dementia Risk over 17 Years of Follow-up among Members of Large Health Care Plan.”

Maria Glymour, ScD

“The elevation in dementia risk with both high and low levels of HDL cholesterol was unexpected, but these increases are small, and their clinical significance is uncertain,” said epidemiologist Maria Glymour, ScD (above), study author and Professor of Epidemiology and Biostatistics at UCSF School of Medicine, in a news release. This is another example of how researchers are associating common biomarkers tested regularly by clinical laboratories with additional health conditions and disease states. (Photo copyright: University of California San Francisco.)

HDL Levels Link to Dementia Risk

The UCSF researchers used cholesterol measurements and health behavior questions as they tracked Kaiser Permanente Northern California health plan members who were at least 55 years old between 2002 and 2007, and who did not have dementia at the time of the study’s launch.

The researchers then followed up with the study participants through December 2020 to find out if they had developed dementia, Medical News Today reported.

“Previous studies on this topic have been inconclusive, and this study is especially informative because of the large number of participants and long follow-up,” said epidemiologist Maria Glymour, ScD, study author and Professor of Epidemiology and Biostatistics at UCSF School of Medicine, in the AAN news release. “This information allowed us to study the links with dementia across the range of cholesterol levels and achieve precise estimates even for people with cholesterol levels that are quite high or quite low.” 

According to HealthDay, UCSF’s study findings included the following:

  • More than 25,000 people developed dementia over about nine years. They were divided into five groups.
  • 53.7 milligrams per deciliter (mg/dL) was the average HDL cholesterol level, amid an optimal range of above 40 mg/dL for men and above 50 mg/dL for women.
  • A 15% rate of dementia was found in participants with HDL of 65 mg/dL or above.
  • A 7% rate of dementia was found in participants with HDL of 11 mg/dL to 41 mg/dL.

“We found a U-shaped relationship between HDL and dementia risk, such that people with either lower or higher HDL had a slightly elevated risk of dementia,” Erin Ferguson, PhD student of Epidemiology at UCSF, the study’s lead study author, told Medical News Today.

What about LDL?

The UCSF researchers found no correlation between low-density lipoprotein (LDL)—often referred to as “bad” cholesterol”—and increased risk for dementia. But the risk did increase slightly when use of statin lipid-lowering medications were included in the analysis.

“Higher LDL was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL was associated with a slightly greater risk of Alzheimer’s disease-related dementia for statin users,” the researchers wrote in Neurology.

“We found no association between LDL cholesterol and dementia risk in the overall study cohort. Our results add to evidence that HDL cholesterol has similarly complex associations with dementia as with heart disease and cancer,” Glymour noted in the AAN news release.

Australian Study also Links High HDL to Dementia

A separate study from Monash University in Melbourne, Victoria, Australia, found that “abnormally high levels” of HDL was also associated with increased risk for dementia, according to a Monash news release.

The Monash study—which was part of the ASPREE (ASPpirin in Reducing Events in the Elderly) trial of people taking daily aspirin—involved 16,703 Australians and 2,411 Americans during the years 2010 to 2014. The researchers found:

  • 850 participants had developed dementia over about six years.
  • A 27% increased risk of dementia among people with HDL above 80 mg/dL and a 42% higher dementia risk for people 75 years and older with high HDL levels.

These findings, Newsweek pointed out, do not necessarily mean that high levels of HDL cause dementia. 

“There might be additional factors that affect both these findings, such as a genetic link that we are currently unaware of,” Andrew Doig, PhD, Professor, Division of Neuroscience at University of Manchester, told Newsweek. Doig was not involved in the in the Monash University research.

Follow-up research could explore the possibility of diagnosing dementia earlier using blood tests and new biomarkers, Newsweek noted.

The Australian researchers published their findings in The Lancet Regional Health-Western Pacific titled, “Association of Plasma High-Density Lipoprotein Cholesterol Level with Risk of Incident Dementia: A Cohort Study of Healthy Older Adults.”

Cholesterol Lab Test Results of Value to Clinical Labs

If further studies validate new biomarkers for testing and diagnosis, a medical laboratory’s longitudinal record of cholesterol test results over many years may be useful in identifying people with an increased risk for dementia.

Clinical pathologists and laboratory managers will want to stay tuned as additional study insights and findings are validated and published. Existing laboratory testing reference ranges may need to be revised as well.

As well, the findings of this UCSF research demonstrate that, in this age of information, there will be plenty of opportunities for clinical lab scientists and pathologists to take their labs’ patient data and combine it with other sets of data. Digital tools like artificial intelligence (AI) and machine learning would then be used to assess that large pool of data and produce clinically actionable insights. In turn, that positions labs to add more value and be paid for that value.

—Donna Marie Pocius

Related Information:

Both High and Low HDL Cholesterol Tied to Increased Risk of Dementia

Low-and High-Density Lipoprotein Cholesterol and Dementia Risk over 17 Years of Follow-up among Members of a Large Health Care Plan

Both High and Low HDL Cholesterol Tied to Slight Increase in Risk of Dementia

How HDL “Good” Cholesterol Might Raise Dementia Risk

HDL vs. LDL Cholesterol

How Levels of “Good” Cholesterol May Increase Dementia Risk

High Levels of “Good Cholesterol” May Be Associated with Dementia Risk, Study Shows

Association of Plasma High-Density Lipoprotein Cholesterol Level with Incident Dementia: A Cohort Study of Healthy Older Adults

Study Claims High Good Cholesterol Levels Linked to Greater Dementia Risk

In Canada, Shortage of Medical Laboratory Technologists and Radiology Technicians Continues to Delay Care

Insights learned from Canada’s experience may benefit clinical laboratories and anatomic pathology groups in the US as well

Canada continues to face a severe shortage of skilled healthcare professionals, especially among medical laboratory technologists (MLTs) and radiology technicians (RTs). According to the Canadian Society for Medical Laboratory Science (CSMLS), “In 2010, the Canadian Institute for Health Information (CIHI) identified that approximately half of all MLTs would be eligible to retire in 10 years, with the greatest impact felt in Canada’s rural and remote communities.” Today, “This staffing concern is currently affecting the professional community across all provinces and territories resulting in the decrease of workers, dramatically impacting organizations and their employees.”

One thing true of government-run healthcare programs is that they consistently underinvest in building new facilities, upgrading older facilities, and training/retaining enough physicians, nurses, and clinical laboratory/radiology workers. This is seen in the UK, Canada, New Zealand, and Australia, where varies combinations of facility, physician, and other healthcare professional shortages generate regular headlines about patient wait times—particularly for elective procedures—that may be six months to a year or more.

For example, officials at Pasqua Hospital in Regina, which serves patients in southern Saskatchewan, Canada, say diagnostics services may need to be shut down by the end of January as a result of “extended, chronic staffing shortages.”

“We’re barely struggling to keep up with urgent cases,” Christy Labreche, a nuclear medicine technologist told the Regina-Leader Post, which noted that people requesting non-urgent treatment may need to make appointments six to 12 weeks out.  

More than 1,500 Saskatchewan residents have been waiting for more than 90 days for computerized tomography (CT) scans, according to the Canadian Union of Public Employees (CUPE).

Pasqua Hospital leaders have asked province officials to take “immediate action,” but they feel their concerns are “falling on deaf ears,” the Leader Post reported.

Bashir Jalloh

“For over a decade, we have been sounding the alarm on behalf of our members that provide a vital service in the continuum of care,” said nuclear medicine technologist Bashir Jalloh (above) in a CUPE statement. Jalloh is President of CUPE 5430, Saskatchewan’s largest healthcare union which represents medical technologists in a variety of specialties. “Now, as waitlists grow, we are at risk of more disruptions of services and communities on bypass for critical care at a time when wait lists are as long as ever.” Clinical laboratory leaders in the US can gain valuable insights from the struggle with shortages taking place in Canada. (Photo copyright: Regina-Leader Post.)

MLT Needs Beyond Saskatchewan

The Canadian Alliance of Medical Laboratory Professionals Regulators (CAMLPR) is working with government authorities on the current and projected countrywide shortage of medical laboratory professionals.

In an article he penned for Today’s Clinical Lab, Adam Chrobak, BSc, MBA, MLT, Registrar/CEO of the College of Medical Laboratory Technologists of Manitoba, and Vice-Chair of the CAMLPR, noted that about 25,600 new medical laboratory jobs will open up by 2031. He pointed out, however, that only about 20,400 people (20% less than what is needed) are expected to pursue those lab jobs, according to employment data from Employment and Social Development Canada, an agency of the Canadian government.

Chrobak noted the following reasons for the deficit of MLTs in Canada:

  • An aging workforce: Many current lab scientists are over age 50, signaling a “potential shortage of medical laboratory technologists when seasoned professionals retire.”
  • Lack of awareness and representation: Other healthcare fields may benefit by being in the public spotlight, while “opportunities and rewards” of a medical lab technology career may not be apparent to job seekers.
  • Insufficient funding for educational programs: The need for laboratory professionals may supersede “scarce healthcare dollars that fund education programs.”
  • Barriers to registration: International applicants may be challenged in “recognition of existing field-of-practice competencies.”

Solutions: Improve Recruitment, Retention

To address the MLT shortages across Canada, CAMLPR aims to step up the registration of people interested in the medical laboratory profession through a project in partnership with the Canadian government called the Flexible Pathways to Registration for Medical Laboratory Technologists. The goal is to develop competency standards for entering the profession, ease the registration process, and increase the supply of qualified health professionals in Canada, according to a news release

This is not the first time Dark Daily has covered Canada’s lab worker shortages. 

In “Clinical Laboratories Suffer During the ‘Great Resignation’,” we reported how the so-called “Great Resignation” caused by the COVID-19 pandemic has had a severe impact on clinical laboratory staffs, creating shortages of pathologists as well as of medical technologists, medical laboratory technicians, and other lab scientists who are vital to clinical laboratories in both Canada and the US.

And in “Lab Staffing Shortages Reaching Dire Levels,” Dark Daily’s sister publication, The Dark Report, noted that CAP Today characterized the current lab staffing shortage as going “from simmer to rolling boil” and that demand for medical technologists and other certified laboratory scientists far exceeds the available supply. Consequently, many labs use overtime and temp workers to handle daily testing, a strategy that has led to staff burnout and a high turnover rate.

Shortages in other areas of Canadian healthcare are on the rise as well, which we covered in “Number of Unfilled Medical Residencies Increases in Alberta and Other Areas of Canada.” We reported that, according to the Angus Reid Institute, approximately half of all Canadians cannot find a doctor or get a timely appointment with their current doctor. And that, just like in many parts of America, certain provinces are experiencing severe medical staffing shortages that includes clinical laboratories and pathology groups.

Global Insights May Offer Ideas  

Dark Daily’s coverage of healthcare industry challenges in Canada, the US, and other countries is aimed at helping clinical laboratory managers and pathologists understand challenges faced by government-run healthcare systems, where there is constant pressure on the government to provide adequate funding. Capital is needed to modernize and expand hospitals and clinics. At the same time, there is need to expand training opportunities to solve the shortage of clinical laboratory scientists, medical laboratory and imaging technologists, doctors, nurses, and other medical professionals.

The insights gained by studying these healthcare systems may be of value to US-based hospitals and medical laboratories that face their own worker recruitment and retention issues. 

—Donna Marie Pocius

Related Information:

Pasqua Hospital Imaging Techs Say Shutdown Imminent Due to Staffing Shortfall

Critical Shortage of Radiological Technologists in Saskatchewan Risks Patient Care

Reduction of Lab and X-ray Services in La Ronge Due to Crisis in Staffing

Saskatchewan Announces $6.9 Billion Healthcare Budget for 2023-24

Solving the Shortage of Medical Laboratory Technologists in Canada

Flexible Pathways to Registration for Medical Laboratory Technologists

Clinical Laboratories Suffer During the ‘Great Resignation’

Lab Staffing Shortages Reaching Dire Levels

Number of Unfilled Medical Residencies Increases in Alberta and Other Areas of Canada

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