News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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100-Biomarker Lab Test for Alzheimer’s Disease Developed by Team at University of Pittsburgh

New clinical laboratory test could replace conventional spinal tap for diagnosing neurodegenerative disease

In a proof-of-concept study, University of Pittsburgh (Pitt) scientists validated a clinical laboratory test that measures more than 100 different genetic sequences associated with Alzheimer’s disease. The Pitt researchers believe the new diagnostic platform could help clinicians “capture the multifaceted nature of Alzheimer’s pathology and streamline early disease diagnostics,” according to a news release.

Clinical laboratory blood tests that detect biomarkers such as phosphorylated tau protein (pTau) have emerged in studies as diagnostic possibilities for Alzheimer’s disease, which is traditionally diagnosed using a lumbar puncture (spinal tap) procedure.

The Pitt scientists published the findings of their study titled, “Multi-Analyte Proteomic Analysis Identifies Blood-based Neuroinflammation, Cerebrovascular, and Synaptic Biomarkers in Preclinical Alzheimer’s Disease,” in the journal Molecular Neurodegeneration.

In their paper, neuroscientist Thomas Karikari, PhD, Assistant Professor of Psychiatry at  University of Pittsburgh, lead author of the study, and his research team acknowledged that progress has been made in detecting Alzheimer’s disease with blood-based biomarkers. However, they note that “two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction.”

The Pitt scientists believe the focus on so-called “classical Alzheimer’s blood biomarkers” limits exploration of neurodegenerative disease.

“Alzheimer’s disease should not be looked at through one single lens. Capturing aspects of Alzheimer’s pathology in a panel of clinically validated biomarkers would increase the likelihood of stopping the disease before any cognitive symptoms emerge,” said neuroscientist Thomas Karikari, PhD (above), Assistant Professor of Psychiatry, University of Pittsburgh, and lead author of the study in a news release. Should further studies prove Pitt’s research sound, clinical laboratories may have a replacement test for diagnosing neurodegenerative disease. (Photo copyright: University of Pittsburgh.)

120 Proteins Analyzed Simultaneously

To conduct their research, the Pitt scientists performed a proof-of-concept study on 176 blood samples from 113 adults in Pennsylvania (average age of 76.7). They analyzed the blood using the NULISAseq CNS (central nervous system) Disease Panel 120 by Alamar Biosciences of Freemont, California.

On its website, Alamar Biosciences explains that the disease panel offers neurological researchers:

  • “Multiplexed analysis of 120 neuro-specific and inflammatory proteins from 10 µl of plasma or CSF (cerebrospinal fluid).
  • Detection of “critical biomarkers—including pTau-217, GFAP (glial fibrillary acidic protein), NEFL (neurofilament light polypeptide) and alpha-synuclein.”

The NULISAseq test works with “a proprietary sequential immunocomplex capture and release mechanism and the latest advances in next-generation sequencing,” according to the company.

Inside Precision Medicine noted that the Alamar Biosciences assay enabled Pitt scientists to detect:

  • Biomarkers (usually found in CSF) “correlating with patients’ amyloid positivity status and changes in amyloid burden over time,” and,
  • Biomarkers including “neuroinflammation, synaptic function, and vascular health, which had not previously been validated in blood samples.”

“The performance of the NULISA platform was independently validated against conventional assays for classic Alzheimer’s biomarkers for each sample. Biomarker profiles over two years were also compared with imaging-based measures of amyloid, tau, and neurodegeneration,” LabMedica reported.

Opportunity to Track Alzheimer’s

Karikari sees the diagnostic platform being used to track individuals’ blood biomarker changes over time. 

In their Molecular Neurodegeneration paper, the Pitt researchers wrote, “These (results) were not limited to markers such as pTau217, p-Tau231, p-Tau181, and GFAP, the elevation of which have consistently shown strong associations with brain Aβ [amyloid beta] and/or tau load, but included novel protein targets that inform about the disease state of the individual in different pathological stages across the biological Alzheimer’s disease continuum.”

About seven million Americans are affected by Alzheimer’s disease, according to the Alzheimer’s Association, which estimated that figure will grow to 13 billion by 2050.

Further studies by Karikari may include larger samples and greater diversity among the people studied, Inside Precision Medicine noted.

“[Karikari’s] lab is developing a predictive model that correlates biomarker changes detected using NULISAseq with brain autopsy data and cognitive assessments collected over the course of several years. Their goal is to identify blood biomarkers that can help stage the disease and predict its progression, both for decision-making around clinical management and treatment plans,” the Pitt news release states.

His research was supported by the National Institute on Aging.

The Pitt scientists have developed a multiplex test that works with 100 different genetic sequences associated with Alzheimer’s. Such advances in the understanding of the human genome are giving scientists the opportunity to combine newly identified gene sequences that have a role in specific disease states.

In turn, as further studies validate the value of these biomarkers for diagnosing disease and guiding treatment decisions, clinical laboratories will have new assays that deliver more value to referring physicians and their patients.

—Donna Marie Pocius

Related Information:

Pitt Scientists Validated a New Panel for Blood Biomarkers of Alzheimer’s

Multi-Analyte Proteomic Analysis Identifies Blood-based Neuroinflammation, Cerebrovascular, and Synaptic Biomarkers in Preclinical Alzheimer’s Disease

Innovative Blood Test Validated for Comprehensive Early Alzheimer’s Diagnosis

New Blood Test Platform Simultaneously Measures Over 100 Biomarkers of Alzheimer’s Disease

Cerebrospinal Fluid and Plasma Tau as a Biomarker for Brain Tauopathy

University of Athens Researchers Create Wooden Tongue Depressor with Biosensing Capabilities Capable of Identifying Biomarkers

Scientists believe the biodegradable device could someday help detect multiple saliva biomarkers. If true, it might provide a new type of test for clinical laboratories

When it comes to tongue depressors, it turns out you can teach an old dog new tricks. Researchers from National and Kapodistrian University of Athens Greece (NKUA) have taken this simple wooden medical tool and developed a high-tech biosensing device that may someday be useful at the point-of-care in hospitals and as a new type of test for clinical laboratories.

Using diode laser engraving, the researchers developed an “eco-friendly disposable sensor that can measure glucose levels and other biomarkers in saliva,” according to LabMedica.

This proof-of-principle biosensing device demonstrates the feasibility of “simultaneous determination of glucose and nitrite in artificial saliva,” according to the NKUA scientists who hope it will help doctors diagnose a variety of conditions.

The researchers published a paper on the development of their new wooden biosensor in the journal Analytical Chemistry titled, “Wooden Tongue Depressor Multiplex Saliva Biosensor Fabricated via Diode Laser Engraving.”

biosensing tongue depressor

In their published paper, the scientists at the University of Athens wrote that their wooden electrochemical biosensing tongue depressor (above) “is an easy-to-fabricate disposable point-of-care chip with a wide scope of applicability to other bioassays,” and that “it paves the way for the low-cost and straightforward production of wooden electrochemical platforms.” Might this and other similar biosensing devices eventually find their way to clinical laboratories for use in identifying and tracking certain biomarkers for disease? (Photo copyright: University of Athens.)


How to Make a High-Tech Tongue Depressor

Though wood is affordable and accessible, it doesn’t conduct electricity very well. The researchers’ first attempt to solve this problem was to use the wood as “a passive substrate” to which they coated “metals and carbon-based inks,” LabMedica reported. After that they tried using high-powered lasers to “char specific regions on the wood, turning those spots into conductive graphite.” But that process was complicated, expensive, and a fire hazard.

The researchers eventually turned to “low-power diode lasers” which have been used successfully “to make polyimide-based sensors but have not previously been applied to wooden electronics and electrochemical sensors,” LabMedica noted.

In their Analytical Chemistry paper, the researchers wrote, “A low-cost laser engraver, equipped with a low-power (0.5 W) diode laser, programmably irradiates the surface of the WTD [wooden tongue depressor], forming two mini electrochemical cells (e-cells). The two e-cells consist of four graphite electrodes: two working electrodes, a common counter, and a common reference electrode. The two e-cells are spatially separated via programmable pen-plotting, using a commercial hydrophobic marker pen.”

In other words, the researchers “used a portable, low-cost laser engraver to create a pattern of conductive graphite electrodes on a wooden tongue depressor, without the need for special conditions. Those electrodes formed two electrochemical cells separated by lines drawn with a water-repellent permanent marker,” states a press release from the American Chemical Society.

“The biosensor was then used to quickly and simultaneously measure nitrite and glucose concentrations in artificial saliva. Nitrite can indicate oral diseases like periodontitis, while glucose can serve as a diagnostic for diabetes. The researchers suggest that these low-cost devices could be adapted to detect other saliva biomarkers and could be easily and rapidly produced on-site at medical facilities,” LabMedica reported.

Benefits of Using Wood

One of the major benefits of using wood for their biosensing device is how environmentally friendly it is. “Since wood is a renewable, biodegradable naturally occurring material, the development of conductive patterns on wood substrates is a new and innovative chapter in sustainable electronics and sensors,” the researchers wrote in Analytical Chemistry.

Additionally, the tongue depressor features “An easy-to-fabricate disposable point-of-care chip with a wide scope of applicability to other bioassays, while it paves the way for the low-cost and straightforward production of wooden electrochemical platforms,” the researchers added.

This adds to a growing trend of developing bioassay products that keep the health of our planet in mind.

In “University of Pennsylvania Researchers Use Cellulose to Produce Accurate Rapid COVID-19 Test Results Faster and Cheaper than Traditional PCR Tests,” we covered how researchers at the University of Pennsylvania (UPenn) had developed a biodegradable rapid COVID-19 test that uses bacterial cellulose (BC) instead of printed circuit boards (PCBs) as its biosensor.

“This new BC test is non-toxic, naturally biodegradable and both inexpensive and scalable to mass production, currently costing less than $4.00 per test to produce. Its cellulose fibers do not require the chemicals used to manufacture paper, and the test is almost entirely biodegradable,” a UPenn blog post noted.

New Future Tool Use in Clinical Diagnostics

Who could have predicted that the lowly wooden tongue depressor would go high tech with technology that uses lasers to convert it to an electrochemical multiplex biosensing device for oral fluid analysis? This is yet another example of technologies cleverly applied to classic devices that enable them to deliver useful diagnostic information about patients.

And while a biosensing tongue depressor is certainly a diagnostic tool that may be useful for nurses and physicians in clinic and hospital settings, with further technology advancements, it could someday be used to collect specimens that measure more than glucose and nitrites.

—Kristin Althea O’Connor

Related Information:

Wooden Tongue Depressor Multiplex Saliva Biosensor Fabricated via Diode Laser Engraving

Say ‘Ahhh’: This Ecofriendly Tongue Depressor Checks Vitals

Biosensor-Fabricated Wooden Tongue Depressor Measures Glucose and Nitrite in Saliva

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