Findings could lead to clinical laboratory test that can both track the disease’s progress and differentiate it from other forms of dementia
Another research study is underway with hopes of developing a new clinical laboratory blood test to aid in the diagnoses of Alzheimer’s disease and help physicians determine the best course of treatment.
Researchers at the Washington University School of Medicine (WashU Medicine) in St. Louis and Lund University in Sweden have developed a test that focuses on the presence of a protein called MTBR-tau243, a potential biomarker for Alzheimer’s. This protein is correlated to the toxic accumulation of tau aggregates in the brain and the severity of the disease, according to a WashU new release.
Cognitive tests and brain imaging are also used to diagnose the condition. However, existing tests cannot establish how far the illness has progressed. Alzheimer’s therapies are most effective during early stages, so determining the disease’s progression could provide insights doctors need to devise the most effective treatment protocols.
Washington University’s new blood test that identifies MTBR-tau243 protein could lead to new biomarkers as well as identifying how far the disease has progressed.
“This blood test clearly identifies Alzheimer’s tau tangles [aka, neurofibrillary tangles], which is our best biomarker measure of Alzheimer’s symptoms and dementia,” said co-senior author Randall J. Bateman, MD, professor of neurology at WashU Medicine in the WashU news release.
“In clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients,” said co-senior author Randall J. Bateman, MD, professor of neurology at WashU Medicine in a news release. (Photo copyright: Washington University.)
Distinguishing between Alzheimer’s and Other Forms of Dementia
The WashU scientists tested the study participants in three main stages of Alzheimer’s disease:
Pre-symptomatic.
Early stage with mild cognitive impairment.
Late symptomatic where patients have been diagnosed with dementia.
The study included 108 volunteers from WashU Medicine’s Charles F. and Joanne Knight Alzheimer Disease Research Center and a subset of 55 people from the Swedish BioFINDER-2 study, which aims to discover key mechanisms in neurodegenerative disorders. The scientists validated their results in an independent dataset involving 739 other people in the BioFINDER-2 database. The patient information used for the study represented patients from all stages of the disease.
Alzheimer’s disease involves an accumulation of amyloid into plaques in the brain, which turn into tangles of tau proteins. When these tau tangles become detectable, cognitive symptoms begin to occur and exacerbate as the tangles spread. WashU’s new blood test can detect MTBR-tau243 levels in the brain with 92% accuracy. The researchers also found that MTBR-tau243 levels were significantly higher for patients in the mild cognitive stage of the disease and up to 200 times higher for patients in the late symptomatic stage.
“MTBR-tau243 is a chipped (off) piece of the protein in Alzheimer’s tau tangles,” Bateman told Medical News Today. “The blood test measures this piece of tau tangles in the blood as a measure of how many tangles are in the brain.”
The researchers also found that MTBR-tau243 levels were normal in patients with cognitive symptoms attributed to diseases other than Alzheimer’s, suggesting that the test can distinguish Alzheimer’s dementia from other forms of dementia.
“We’re about to enter the era of personalized medicine for Alzheimer’s disease,” said Kanta Horie, PhD, voluntary research associate professor of neurology at WashU Medicine, co-first and co-corresponding author of the study, in the WashU news release.
More Studies Needed
According to the Centers for Disease Control and Prevention (CDC), Alzheimer’s is the seventh leading causes of death in the US. It accounted for more than 120,000 deaths in 2022, the most recent year for available data. With the ebbing of COVID-19, which was ranked number four in 2022, Alzheimer’s is assumed to be higher in ranking for more recent years.
Washington University’s new blood test for Alzheimer’s may one day enable earlier detection of the disease, earlier intervention, and slowing of its advancement. However, more research and trials are needed into the theory behind this study.
“The initial study needs to be replicated in larger and more diverse populations to confirm its accuracy and reliability across different demographics, ethnicities, and stages of the disease,” Manisha Parulekar, MD, director of the Division of Geriatrics at Hackensack University Medical Center, told Medical News Today. “This includes testing individuals with other neurological conditions to ensure specificity. Clear and standardized protocols for blood collection, processing, and analysis must be established to ensure consistent and reproducible results across different laboratories and healthcare settings.”
Painless technology could one day replace some phlebotomy blood draws as the go-to specimen-collection method for clinical laboratory testing and health monitoring
Clinical laboratories have long sought a non-invasive way to do useful medical laboratory testing without the need for either a venipuncture or a needle stick. Now engineers at the McKelvey School of Engineering at Washington University in St. Louis in Missouri have developed a disposable microneedle patch that one day could be a painless alternative to some blood draws for diagnostics tests and health monitoring.
The technology uses an easy-to-administer low-cost patch that can be applied to the skin like an adhesive bandage. The patch is virtually painless because the microneedles are too small to reach nerve receptors. Another unique aspect to this innovative approach to collecting a specimen for diagnostic testing is that the Washington University in St. Louis (WashU) research team designed the microneedle patch to include plasmonic-fluor. These are ultrabright gold nanolabels that light up target protein biomarkers and can make the biomarkers up to 1,400 times brighter at low concentrations, compared to traditional fluorescent labels.
The patch, states a WashU news release, “… can be applied to the skin, capture a biomarker of interest and, thanks to its unprecedented sensitivity, allow clinicians to detect its presence.”
The technology is low cost, easy for clinicians or patients themselves to use, and could eliminate the need for a trip to patient service center where a phlebotomist would draw blood for clinical laboratory testing, the news release states.
“We have created a platform technology that anyone can use. And they can use it to find their own biomarker of interest,” study leader Srikanth Singamaneni, PhD (above), Lilyan and E. Lisle Hughes Professor in the Department of Mechanical Engineering and Materials Sciences at Washington University in St. Louis, said in the WashU news release. Singamaneni and his colleagues are developing a new specimen collection method that might someday be widely used by clinical laboratories. (Photo copyright: Washington University in St. Louis.)
“We used the microneedle patch in mice for minimally invasive evaluation of the efficiency of a cocaine vaccine, for longitudinal monitoring of the levels of inflammatory biomarkers, and for efficient sampling of the calvarial periosteum [a skull membrane]—a challenging site for biomarker detection—and the quantification of its levels of the matricellular protein periostin, which cannot be accurately inferred from blood or other systemic biofluids,” the researchers wrote. “Microneedle patches for the minimally invasive collection and analysis of biomarkers in interstitial fluid might facilitate point-of-care diagnostics and longitudinal monitoring.”
Mark Prausnitz, PhD, Regents’ Professor, J. Erskine Love Jr. Chair in Chemical and Biomolecular Engineering, and Director of the Center for Drug Design, Development, and Delivery at Georgia Tech, told WIRED, “Blood is a tiny fraction of the fluid in our body. Other fluids should have something useful—it’s just hard to get those fluids.”
“Previously, concentrations of a biomarker had to be on the order of a few micrograms per milliliter of fluid,” said Zheyu (Ryan) Wang, a PhD candidate in Srikanth Singamaneni’s lab at McKelvey School of Engineering and a lead author of the paper, in the WashU news release. By using plasmonic-fluor, researchers were able to detect biomarkers on the order of picograms per milliliter—one millionth of the concentration.
“That’s orders of magnitude more sensitive,” Wang said.
Unlike blood, dermal interstitial fluid often does not contain high enough concentrations of biomarkers to be easily detectable. To overcome this hurdle, the Washington University in St. Louis research team developed a microneedle patch with plasmonic-fluor—ultrabright gold nanolabels (above)—which lit up target protein biomarkers, making them roughly 1,400 times brighter at low concentrations than when using traditional fluorescent labels commonly used in many medical laboratory tests. (Photo copyright: Washington University in St. Louis.)
Can Microneedles Be Used as a Diagnostic Tool?
As reported in WIRED, the polystyrene patch developed by Srikanth Singamaneni’s lab at McKelvey School of Engineering removes interstitial fluid from the skin and turns the needles into “biomarker traps” by coating them with antibodies known to bind to specific proteins, such as Interleukin 6 (IL-6). Once the microneedles are mixed with plasmonic-fluor, the patch will glow if the IL-6 biomarkers are present.
The development of such a highly sensitive biomarker-detection method means skin becomes a potential pathway for using microneedles to diagnose conditions, such as myocardial infarction or to measure COVID-19 antibodies in vaccinated persons.
“Now we can actually use this tool to understand what’s going on with interstitial fluid, and how we’re going to be able to use it to answer healthcare-related or medical problems,” Maral Mousavi, PhD, Assistant Professor of Biomedical Engineering, Viterbi School of Engineering at the University of Southern California, told WIRED. “I think it has the potential to be that kind of a game changer.”
Because the WashU study is a proof-of-concept in mice, it may be many years before this technology finds its way to clinical application. Many skin biomarkers will need to be verified for direct links to disease before microneedle patches will be of practical use to clinicians for diagnostics. However, microneedle patch technology has already proven viable for the collection of blood.
In 2017, Massachusetts-based Seventh Sense Biosystems (7SBio) received 510(k) clearance for a new microneedle blood collection device. Called TAP, the device is placed on the upper arm and blood collection starts with a press of a button. The process takes two to three minutes.
Initially, the FDA clearance permitted only healthcare workers to use the device “to collect capillary blood for hemoglobin A1c (HbA1c) testing, which is routinely used to monitor blood sugar levels in diabetic or pre-diabetic patients,” a Flagship Pioneering news release noted.
Then, in 2019, the FDA extended its authorization “to include blood collection by laypersons. Regulators are also allowing the device to be used ‘at-home’ for wellness testing,” a 7SBio news release stated. This opened the door for a microneedle device to be used for home care blood collection.
“No one likes getting blood drawn, but blood is the single-most important source of medical information in healthcare today, with about 90% of all diagnostic information coming from blood and its components,” Howard Weisman, former CEO of 7SBio and current CEO of PaxMedica, a clinical-stage biopharmaceutical company, said in the Flagship Pioneering news release. “TAP has the potential to transform blood collection from an inconvenient, stressful, and painful experience to one people can do themselves anywhere, making health monitoring much easier for both healthcare professionals and patients.”
As microneedle technology continues to evolve, clinical laboratories should expect patches to be used in a growing number of drug delivery systems and diagnostic tests. But further research will be needed to determine whether interstitial fluid can provide an alternate pathway for diagnosing disease.
