Blood test for identifying marker of Alzheimer's disease

At the Alzheimer's Association International Conference, July 2017, Dr. Randall Bateman presented data showing that amyloid beta (Abeta) concentrations can be measured reliably using mass spectrometry, and that the ratio between two of the Abeta isoforms measured in plasma can be used to indicate if a person has brain amyloidosis - a hallmark pathology observed in patients with Alzheimer's disease. Alzforum Coverage

Washington University School of Medicine Press Release

Alzheimer's Association Press Release


NIH Director Highlights Tau Diagnostic Technology

On May 2nd 2017, the NIH Director, Sir Francis Collins, highlighted the recently published study by Washington University scientists in collaboration with C2N Diagnostics, showing that the protein tau increases in blood after peripheral administration of an anti-tau antibody. The study found that, in mice, the level of tau increase in blood correlated with the tau pathology in the brain, raising the possibility that this technology could be used to develop a blood test for brain tau pathology.

C2N tracking technology finds Alzheimer's faster

May 6, 2011, Saint Louis Business Journal

Local biotech startup C2N Diagnostics LLC is leading the way in finding new, more effective treatments for Alzheimer’s disease and other disorders through a unique metabolic labeling technology.

The technology, stable isotope-linked kinetics (SILK), was discovered at Washington University School of Medicine by Drs. Randall Bateman and David Holtzman. The technique allows tracking of the brain’s production and clearance of amyloid beta, a protein that’s closely linked to the disease. This gives scientists insights into the progression of the disease and enables physicians to start an effective course of treatment before the patient exhibits clinical symptoms.

Read more: C2N tracking technology finds Alzheimer's faster | St. Louis Business Journal

A recent media perspective on C2N Diagnostics

April 1, 2011, Healthcare Digital

A new series from HEC-TV showcases the role of C2N's technology in exploring questions about the origins of Alzheimer's Disease

C2N is an emerging biomarkers company out of the St. Louis region. The company serves as a good example of the contributions that start-up companies can provide to society based on important technologies developed within the laboratories of academic centers.

The Link below is an innovations program that the Higher Education Channel out of St. Louis just recently televised.

The fourth segment of the show (beginning at 20 mins 35 secs) covers Dr. Randall Bateman's (one of C2N's two scientific co-founders) Alzheimer's research work at Washington University, along with work that is ongoing at C2N. C2N is commercializing a suite of biomarkers that intend to speed the development of therapeutics and diagnostics for serious disorders affecting the central nervous system and cognition.

C2N Diagnostics, Probing the Markers of Disease

April, 2011, Business Review USA

C2N Diagnostics is at the forefront of innovation and technology with respect to the analysis of how neurodegenerative disorders impair normal biological processes within the brain. The tools developed and deployed at C2N allow for the rapid testing of new drugs in development, designed to prevent or revert underlying disease processes.

C2N Diagnostics offers a portfolio of bioanalytical research services and tools to pharmaceutical and biotechnology companies. These companies employ C2N to evaluate new therapies in development for brain disorders like Alzheimer’s and Parkinson’s diseases. C2N also applies its technology to better understand the causes of these diseases and to enable their early stage detection.

Company profile

Company brochure

SILK-Ab™ Assay Provides New Insights Into the Potential Origins of Alzheimer’s Disease

December 10, 2010 C2N Diagnostics co-founding scientist – Dr. Randall Bateman – and colleagues at Washington University School of Medicine publish key findings in online edition of Science

ST. LOUIS, MO – C2N Diagnostics announced today that one of its co-founding scientists, Dr. Randall Bateman, and his colleagues from the Washington University School of Medicine have independently authored an article that appeared in yesterday’s online edition of Science. The publication, entitled “Decreased Clearance of CNS Amyloid-b in Alzheimer’s Disease”, sheds important new light into the potential origins of late-onset, or sporadic, Alzheimer’s Disease (AD). The findings may also aid in the future development of an early diagnostic test and target for effective drug therapy.

Amyloid-beta (Ab) is a protein fragment found in plaques within the brains of individuals with dementia due to AD. It is believed that excessive levels of Ab are toxic to brain cells and a potential key mediator of AD progression. Historically, the reasons for the accumulation of Ab plaques in patients with sporadic AD have been poorly understood. A common presumption is that AD may result from an over-production of the protein fragment.

The new study provides an important piece of evidence that AD may result from a defect in the clearance, or removal, of Ab from the brain rather than from its over-production. Dr. Bateman and his colleagues used the stable-isotope labeling kinetics (SILK) assay platform currently commercialized by C2N and licensed from Washington University, to measure the production and clearance rates of the Ab marker isolated from the cerebrospinal fluid (CSF) of 24 individuals. Study subjects fell into one of two groups: those with late-onset, symptomatic AD, and those who were cognitively normal, but of comparable age. The mean age of the individuals tested was 74 years.

Individuals with late-onset AD had no impairment in their production rate of Ab. Strikingly, however, these individuals on average had an approximate 30% lower clearance rate relative to those who were cognitively normal. The results achieved statistical significance, implying that the findings were very unlikely due to a chance observation. Per the authors, these data suggest that “Ab clearance mechanisms may be critically important in the development of AD.” Based on the magnitude of the observed clearance defect, the authors also suggested that “brain Ab accumulates over approximately 10 years” before the time of onset of the symptoms of AD.

Stated Dr. Joel Braunstein, managing member of C2N, “We are very proud of Dr. Bateman and his colleagues for their important contributions to the field. Hopefully, the findings from this study will advance the research community’s efforts to develop agents that will modify the underlying biology of AD, while potentially creating an opportunity for earlier disease detection through the use of effective biomarkers. Early intervention is likely to afford the greatest clinical benefit to patients at high risk for symptomatic AD.”


Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ. Decreased clearance of CNS amyloid-beta in Alzheimer's disease. Science Express, Dec. 9, 2010.

About Alzheimer’s Disease

Alzheimer’s disease is a progressive neurological disorder characterized by loss of memory and decline in basic mental ability. Though several drugs are available to treat the symptoms of Alzheimer’s, none halt or modify disease progression. The risk of developing Alzheimer’s disease increases significantly with age. By the age of 85, approximately 1 out of 2 people likely have the disease. Alzheimer’s disease affects more than 20 million elderly people worldwide, and the incidence is likely to grow rapidly over the following decades. According to the Alzheimer’s Research Trust, an estimated 4.6 million new cases of Alzheimer’s are diagnosed each year worldwide, and roughly 500,000 of these occur in the United States alone.

About C2N Diagnostics

C2N Diagnostics, LLC formed in late 2007 by scientific co-founders Drs. David Holtzman and Randall Bateman of Washington University School of Medicine in St. Louis, the Washington University Office of Technology Management, and LifeTech Research, a Maryland-based technology research and commercialization firm ( C2N resides at the Center for Emerging Technologies in St. Louis. The company is developing a suite of biomarker assays and tools to assist in pre-clinical drug discovery, clinical drug development, and the early detection and assessment of progression of debilitating neurodegenerative disorders. The SILK-Aß™ assay, relies on stable isotope labeling and tandem mass spectrometry for the precise measurement of the kinetics, or in vivo metabolism, of amyloid-beta – a small peptide implicated as a key mediator of Alzheimer’s disease. Other products are in development to target Parkinson’s disease, Huntington’s disease, schizophrenia, and amyotrophic lateral sclerosis (ALS), among others. For additional information, see or call 1-877-C2N-DIAG (1-877-226-3424).

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Cutting health cost helps new ideas sell

April 21, 2010, St. Louis Post Dispatch

From St. Louis Post Dispatch:

Another local startup, C2N Diagnostics, is working with pharmaceutical companies to develop a test that can detect Alzheimer's at its earliest stages and also to guide effective treatment before patients manifest clinical symptoms. By the time symptoms are observed, neurological damage has occurred. So the goal is to catch Alzheimer's early — to delay or prevent symptoms in someone who has a high risk of developing it in the future.

"We need better measurements and tools to both discover drugs for Alzheimer's as well as to develop them clinically," said Joel Braunstein, a co-founder of C2N.

Cutting health care costs is just one of the messages pitched by medical entrepreneurs to investors.

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David Holtzman: Attacking Alzheimer's With a New Test for Amyloid Beta

June 30, 2009, U.S. News and World Report

Neuroscientist David Holtzman was captivated by Alzheimer's disease as a medical student. Now the 47-year-old associate director of the Alzheimer's Disease Research Center at the Washington University School of Medicine in St. Louis, Holtzman says he realized that Alzheimer's "was going to be one of the biggest problems that we would face, and it was unsolved." Figuring out how the illness begins and how to prevent or slow it has been his goal ever since.

Holtzman's persistence is paying off. Until now, it typically took about two years to determine whether a new Alzheimer's drug was having an effect. But recently, he and colleagues devised a test that rapidly shows whether an experimental medication has a chance of working. "There aren't good ways without doing a long, expensive trial" to determine this, he says. But with the new test, called stable isotope-linked kinetics, or SILK, "we were able to come up with a technique to figure out over a day or two whether a drug is hitting its target in the brain," he says.

SILK reveals whether the medication is limiting production of amyloid beta, a substance that can lead to the formation of plaques on the brains of Alzheimer's patients. The test is the first that directly measures the rate at which amyloid beta is produced and how quickly it is cleared from the brain. Small amounts of amyloid beta are generated as an ordinary metabolic byproduct and are believed to do no harm, but larger amounts seem to be tied to Alzheimer's.

His lab also is investigating how to manipulate the most important genetic risk factor for Alzheimer's, a protein called APOE, in hopes of treating the disease. "He's clearly one of the leaders in Alzheimer's disease research," says Stephen Snyder, deputy director of the division of neuroscience at the National Institute on Aging. "He's really sort of set a pace, a research agenda."

Holtzman, who also chairs the medical school's neurology department, would prefer not to focus on treating the disease. His greatest hope is for researchers to recognize that the disease "starts before the symptoms and signs." That way, he says, "we can work on prevention."

Washington University neurologists create Alzheimer’s drug test

April 10, 2009, St. Louis Business Journal Washington University School of Medicine researchers have developed a test that may help assess more quickly the ability of Alzheimer's drugs to affect one of the possible underlying causes of Alzheimer's disease in humans.

Scientists used the test to show that an Alzheimer's drug in clinical trials by Eli Lilly reduced in healthy volunteers the production of a substance known as amyloid beta (A-beta), a normal byproduct of human metabolism that builds to unhealthy levels forming brain plaques in Alzheimer's patients.

Washington University researchers wanted to see whether a new measurement technique, stable isotope-linked kinetics (SILK), could detect the study drug's impact on A-beta synthesis in healthy volunteers. The results appeared Friday in the Annals of Neurology.

The study was funded through a Lilly grant from a funding program that allowed Bateman to propose the research and retain control of it. Five of the paper's 12 authors are Eli Lilly employees. Dr. Randall Bateman, a Washington U. neurologist, is the study’s director. Washington University licensed its pending patents on SILK to C2N Diagnostics, a St. Louis diagnostics company started by Bateman, and Dr. David Holtzman, Washington U. chair of neurology.

Bateman and Holtzman's financial interests in the company are governed by the university's conflict-of-interest policies, the university said.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals.

From St. Louis Business Journal