amyloid-beta protein Archives

New Washington University Medicine Blood Test Can Diagnose and Track Progression of Alzheimer’s Disease with 92% Accuracy

May 23, 2025 | International Laboratory News, Laboratory Pathology, Laboratory Resources, Laboratory Testing, Precision Medicine

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.

The researchers published their findings in the journal Nature Medicine titled, “Plasma MTBR-tau243 Biomarker Identifies Tau Tangle Pathology in Alzheimer’s Disease.”

“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.”

—JP Schlingman

New Research Challenges Long-Held Theory about Causes of Alzheimer’s Disease, Creating the Possibility of Useful New Biomarkers for Clinical Laboratory Tests

Dec 7, 2022 | Digital Pathology, International Laboratory News, Laboratory Pathology, Laboratory Resources, Laboratory Testing, Precision Medicine

University of Cincinnati researchers hypothesize that low levels of amyloid-beta protein, not amyloid plaques, are to blame

New research from the University of Cincinnati (UC) and Karolinska Institute in Sweden challenges the prevailing theory about the causes of Alzheimer’s disease, suggesting the possibility of new avenues for the development of effective clinical laboratory assays, as well as effective therapies for treating patients diagnosed with Alzheimer’s.

Scientists have long theorized that the disease is caused by a buildup of amyloid plaques in the brain. These plaques are hardened forms of the amyloid-beta protein, according to a UC news story.

However, in their findings published in the Journal of Alzheimer’s Disease, titled “High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations,” the researchers advanced an alternative hypothesis—that Alzheimer’s is instead caused by “depletion” of a soluble form of that same amyloid-beta protein.

“The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia,” said Alberto Espay, MD, one of the lead researchers of the study, in another UC news story. Espay is Professor of Neurology at the UC College of Medicine and Director and Endowed Chair of the Gardner Center for Parkinson’s Disease and Movement Disorders.

“Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies,” he added.

“It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques,” said Alberto Espay, MD (above), in a University of Cincinnati news story. “Degeneration is a process of loss, and what we lose turns out to be much more important.” The UC study could lead to new clinical laboratory diagnostics, as well as treatments for Alzheimer’s and Parkinson’s diseases. (Photo copyright: University of Cincinnati.)

High Levels of Aβ42 Associated with Lower Dementia Risk

In their retrospective longitudinal study, the UC researchers looked at clinical assessments of individuals participating in the Dominantly Inherited Alzheimer Network (DIAN) cohort study. DIAN is an ongoing effort, sponsored by the Washington University School of Medicine in St. Louis, to identify biomarkers associated with Alzheimer’s among people who carry Alzheimer’s mutations.

The researchers found that study participants with high levels of a soluble amyloid-beta protein, Aβ42, were less likely to develop dementia than those with lower levels of the protein, regardless of the levels of amyloid plaques in their brains or the amount of tau protein—either as phosphorylated tau (p-tau) or total tau (t-tau)—in their cerebral spinal fluid. P-tau and t-tau are proteins that form “tau tangles” in the brain that are also associated with Alzheimer’s.

One limitation of the study was that the researchers were unable to include Aβ40, another amyloid-beta protein, in their analysis. But they noted that this “did not limit the testing of our hypothesis since Aβ40 exhibits lower fibrillogenicity and lesser depletion than Aβ42, and is therefore less relevant to the process of protein aggregation than Aβ42.” Fibrillogenicity, in this context, refers to the process by which the amyloid-beta protein hardens into plaque.

While the presence of plaques may be correlated with Alzheimer’s, “Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing,” UC news stated. “These levels decrease because the normal protein, under situations of biological, metabolic, or infectious stress, transform into the abnormal amyloid plaques.”

The UC News story also noted that many attempts to develop therapeutics for Alzheimer’s have focused on reducing amyloid plaques, but “in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.”

New Therapeutics for Multiple Neurodegenerative Diseases

Eisai, a Japanese pharmaceutical company, recently announced phase three clinical trial results of lecanemab, an experimental drug jointly developed by Eisai and Biogen, claiming that the experimental Alzheimer’s drug modestly reduced cognitive decline in early-stage patients, according to NBC News.

Espay noted that lecanemab “does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta.” That may slow the process of soluble proteins hardening into plaques.

Beyond their findings about Alzheimer’s, the researchers believe similar mechanisms could be at work in other neurodegenerative diseases such as Parkinson’s disease, where the soluble alpha-synuclein protein also hardens into deposits.

“We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins,” Espay said. “The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”

Espay foresees two approaches to treating these diseases: Rescue medicine, perhaps based on increasing levels of important proteins, and precision medicine, which “entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle, or a biological or genetic process,” according to UC News. “If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.”

Clinical Laboratory Impact

What does this mean for clinical laboratories engaged in treatment of both Alzheimer’s and Parkinson’s patients? A new understanding of the disease would create “the opportunity to identify new biomarkers and create new clinical laboratory tests that may help diagnose Alzheimer’s earlier in the disease progression, along with tests that help with the patient’s prognosis and monitoring his or her progression,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.

Given the incidence of Alzheimer’s disease in the population, any clinical laboratory test cleared by the FDA would be a frequently-ordered assay, Michel noted. It also would create the opportunity for pathologists and clinical laboratories to provide valuable interpretation about the test results to the ordering physicians.

—Stephen Beale

Related Information:

High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations

UC Study: Decreased Proteins, Not Amyloid Plaques, Tied to Alzheimer’s Disease

US News: Scientists Propose New Mechanism Driving Alzheimer’s

Scientists Propose New Mechanism Driving Alzheimer’s Disease

Alzheimer’s: Lack of Beta-Amyloid, Not Plaque Buildup, May Be the Culprit

Better Cognitive Predictor in People at High Risk of Alzheimer’s Disease

UC Study: Researchers Question Prevailing Alzheimer’s Theory with New Discovery

ABPP Amyloid Plaques’ Role in Onset of Alzheimer’s Questioned by Cincinnati University: GlobalData Reveals That ABPP Targeted by a Tenth of All Alzheimer’s Drugs

Blots on a Field? A Neuroscience Image Sleuth Finds Signs of Fabrication in Scores of Alzheimer’s Articles, Threatening a Reigning Theory of the Disease

WVXU: Does a Key Alzheimer’s Study Contain Fabricated Images?