Excitement and anticipation are building for the use of blood tests to detect Alzheimer’s Disease. A recent article in the Washington Post detailed the work of GHR partner C2N Diagnostics and the groundbreaking research of its co-founder, Dr. Randall Bateman.

From The Washington Post:

“For C2N, the journey to this moment began years ago. It started, like many advances in science, with a few seemingly simple questions that Bateman, then a postdoctoral research fellow, asked Holtzman, his mentor. Why do people — but not other mammals — get amyloid plaques in their brains? Is the protein accumulating and not being cleared? In 2004, Bateman launched a groundbreaking experiment to measure how quickly amyloid is produced and cleared by the brain. For 36 hours, spinal catheters collected cerebrospinal fluid from several participants, some of whom had Alzheimer’s. Bateman served as his own first subject. The study showed that Alzheimer’s patients produced amyloid beta at the same rate as other people but cleared it more slowly. Bateman theorized that the clearance rates might form the basis for a diagnostic test, but ultimately went in a different direction. Brain abnormalities develop 10 to 20 years before symptoms emerge, suggesting people might be able to take steps to delay or prevent the disease. Blood tests could alert individuals to their risks, allowing them to receive a preventive therapy, if one is developed, or pursue better exercise and diet.”

Read more on the the Alzheimer's blood test research landscape.

GHR’s goal is to help patients and families live full lives in a world where Alzheimer’s Disease becomes a preventable condition. GHR aims to halt Alzheimer's disease prior to the onset of cognitive symptoms by supporting new diagnostic tools and prevention trials. Learn more about our work on Alzheimer’s prevention.

GHR partner C₂N Diagnostics, a leader in advanced brain health diagnostics, has entered several important partnerships in the last quarter that will advance access to its PrecivityAD blood test. The PrecivityAD test is an innovative new blood test intended for use in patients with cognitive impairment. The test aims to help healthcare providers determine the presence or absence of amyloid plaques in the brain, a hallmark sign of Alzheimer’s disease.

Two of these new partnerships expand access to the test in Brazil and Australia. In Brazil, C2N is partnering with Grupo Fleury, one of Brazil’s leading healthcare companies. The partnership will introduce the most advanced set of plasma biomarkers to detect changes that indicate the presence of Alzheimer’s disease pathology in patients experiencing memory difficulties. In Australia, a partnership with Healius Ltd, one of Australia's leading listed healthcare companies, will enable the use of C₂N’s PrecivityAD blood test and related brain health biomarkers in memory and dementia care.

In addition, C2N and Eisai, Inc. are partnering to build awareness about how blood-based assays for cognitive impairment, including Alzheimer’s disease (AD), may help patients receive a timely diagnosis and appropriate treatment, especially in traditionally underserved communities. The development and adoption of blood-based assays in everyday clinical practice is an important step in improving care for people in remote and underserved communities where access to the traditional diagnostic tools of positron emission tomography (PET) and lumbar punctures are not viable options. 

C₂N Diagnostics’ Alzheimer's blood test was introduced into the clinic in October of 2020, a breakthrough healthcare innovation for patients, advocates, and physicians who have long awaited an easy to administer test that can help them better understand Alzheimer’s disease. 

Learn more about C₂N Diagnostics’ partnerships.

An air of optimism marked the Alzheimer’s Association International Conference (AAIC) in San Diego last week, as over 9,000 scientists joined in-person and virtually to share research discoveries, connect with their peers and learn from others. Several presenters highlighted the exciting potential of recent scientific developments, considered almost impossible to conceive of five or ten years ago. Today, the scientific community can completely remove amyloid plaque in the brain as measured by PET scans – the buildup of which is considered a precursor to Alzheimer’s Disease. New blood biomarkers offer greater understanding and ability to detect disease, without the cost and invasiveness of alternative testing procedures. Finally, prevention therapy offers the potential to treat Alzheimer’s patients ten to twenty years before the onset of symptoms.

The Alzheimer’s Association is a valued partner in our shared journey to find a way to prevent Alzheimer’s Disease and related dementias. Together, we have provided key philanthropic support to prevention trials in early onset families and in the general population. 
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You can review the news highlights from AAIC and press releases to learn more about the exciting discoveries shared at AAIC 2022.

From Nature:

"Aisen foresees a future — maybe just a decade or so down the line — in which much of the burden of Alzheimer’s disease might actually be prevented. “We’re heading towards screening people from middle age on with blood tests, and treating those who show amyloid abnormalities with drugs that reduce the generation of amyloid plaques,” he says. “I am optimistic.”

A lot needs to go right for this hopeful view to become reality. Large clinical trials will have to show that these therapies work, and amyloid-clearing drugs will have to be proven to be safe and affordable. After decades of setbacks and failed clinical trials, some dementia researchers prefer to express caution. “The field is taking tremendous risks by engaging in studies that can cost billions of dollars,” says neurologist David Knopman at the Mayo Clinic in Rochester, Minnesota.

It will take a while for answers to emerge. Some trials of Alzheimer’s disease prevention are just getting started, and some ongoing ones could stretch into the next decade."

Read more. 

C2N Diagnostics’ Alzheimer's blood test was introduced into the clinic in October of 2020, a breakthrough healthcare innovation for patients, advocates, and physicians who have long awaited an easy to administer test that can help them better understand Alzheimer’s disease. C2N developed this groundbreaking test based upon longtime GHR partner Dr. Randall Bateman’s initial discovery of how to measure amyloid proteins in blood, validating its results in a clinical trial of 686 patients. 

From C2N Diagnostics: 

"C2N Diagnostics today announced its latest innovative offering for enhancing care in brain health: a high-resolution mass spectrometry-based plasma tau multi-analyte assay (p-tau MAA) for Research Use Only (RUO). 

This assay uses a small sample of blood to precisely and simultaneously measure different phosphorylated and nonphosphorylated forms of the tau protein, including forms with phosphorylation at the tau217 and tau181 sites. The assay draws upon prior discoveries by medical researchers that complex interactions among abnormal tau and beta-amyloid proteins and several other factors play a vital role in Alzheimer’s-related brain changes."

​Read more. 

From the NIH National Institute on Aging:

"As we mark the 10-year anniversary of the National Plan to Address Alzheimer’s Disease, which arose from the National Alzheimer's Project Act (NAPA), it’s striking to pause for a moment and consider how far we have come. Thanks to increased congressional funding, NIH spending on Alzheimer’s and related dementias research advanced nearly 4.5-fold between fiscal years 2015 and 2020, reaching $2.87 billion. This momentum has enabled NIA-funded science to take significant strides forward.

NIA small business innovation research funding helped validate and commercialize the PrecivityAD™ test, a more affordable and less invasive alternative to traditional Alzheimer’s tests like spinal taps or brain scans. This blood biomarker-based test is now widely available to doctors and researchers across the United States."

​Read more.

From the National Institute on Aging at NIH:
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Scientists have demonstrated that a new blood test can accurately predict the presence of beta-amyloid plaques in the brain, according to a new study funded in part by NIA. Published in Neurology, the study analyzed the ability of a blood test to predict the presence of Alzheimer’s disease-associated protein beta-amyloid in the brain. The new blood test, which performs comparably to existing brain scan- or spinal tap-based tests, could lower costs and expand the availability of diagnostic studies for Alzheimer’s disease.

Read more.

.From USA Today:

• New blood tests could offer easier way to detect signs of the disease in older adults with memory issues
• The tests may be helpful in identifying subjects for clinical trials or to screen for treatment.
• Alzheimer’s disease afflicts an estimated 6.5 million Americans.

As pharmaceutical companies spend hundreds of millions of dollars on a potential treatment for Alzheimer’s disease, other researchers are focusing on a more elemental question.

How can you tell whether a family member or loved one has Alzheimer’s or another form of dementia?

Read more.

A blood test developed at Washington University School of Medicine in St. Louis has proven highly accurate in detecting early signs of Alzheimer’s disease in a study involving nearly 500 patients from across three continents, providing further evidence that the test should be considered for routine screening and diagnosis.

The study is available in the journal Neurology.

“Our study shows that the blood test provides a robust measure for detecting amyloid plaques associated with Alzheimer’s disease, even among patients not yet experiencing cognitive declines,” said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology.

“A blood test for Alzheimer’s provides a huge boost for Alzheimer’s research and diagnosis, drastically cutting the time and cost of identifying patients for clinical trials and spurring the development of new treatment options,” Bateman said. “As new drugs become available, a blood test could determine who might benefit from treatment, including those at very early stages of the disease.”

Developed by Bateman and colleagues, the blood test assesses whether amyloid plaques have begun accumulating in the brain based on the ratio of the levels of the amyloid beta proteins Aβ42 and Aβ40 in the blood.

Researchers have long pursued a low-cost, easily accessible blood test for Alzheimer’s as an alternative to the expensive brain scans and invasive spinal taps now used to assess the presence and progression of the disease within the brain.

Evaluating the disease using PET brain scans – still the gold standard – requires a radioactive brain scan, at an average cost of $5,000 to $8,000 per scan. Another common test, which analyzes levels of amyloid-beta and tau protein in cerebrospinal fluid, costs about $1,000 but requires a spinal tap process that some patients may be unwilling to endure.

This study estimates that prescreening with a $500 blood test could reduce by half both the cost and the time it takes to enroll patients in clinical trials that use PET scans. Screening with blood tests alone could be completed in less than six months and cut costs by tenfold or more, the study finds.

A commercial test based on Bateman’s research was certified in 2020 under the Clinical Laboratory Improvement Amendments (CLIA) program. The CLIA certification program is run by the Food and Drug Administration in partnership with the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services.

Known as Precivity AD, the commercial version of the test is marketed by C2N Diagnostics, a Washington University startup founded by Bateman and his colleague David Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology. Bateman and Holtzman are inventors on a patent the university licensed to C2N.

CLIA certification makes the test available for doctors in the United States. It is intended to provide information that will aid the medical evaluation and care of patients who already have symptoms of cognitive decline. A similar certification makes the test available in Europe. The test is not yet covered by most health insurance.

The current study shows that the blood test remains highly accurate, even when performed in different labs following different protocols, and in different cohorts across three continents.

Scientists didn’t know if small differences in sampling methods, such as whether blood is collected after fasting or the type of anti-coagulant used in blood processing, could have a big impact on test accuracy because results are based on subtle shifts in amyloid beta protein levels in the blood. Differences that interfere with the precise measurement of these amyloid protein ratios could have triggered a false negative or positive result.

To confirm the test’s accuracy, researchers applied it to blood samples from individuals enrolled in ongoing Alzheimer’s studies in the United States, Australia and Sweden, each of which uses different protocols for the processing of blood samples and related brain imaging.

Findings from this study confirmed that the Aβ42/Aβ40 blood test using a high-precision immunoprecipitation mass spectrometry technique developed at Washington University provides highly accurate and consistent results for both cognitively impaired and unimpaired individuals across all three studies.

When blood amyloid levels were combined with another major Alzheimer’s risk factor – the presence of the genetic variant APOE4 – the accuracy of the blood test was 88% when compared to brain imaging and 93% when compared to spinal tap.

“These results suggest the test can be useful in identifying nonimpaired patients who may be at risk for future dementia, offering them the opportunity to get enrolled in clinical trials when early intervention has the potential to do the most good,” Bateman said. “A negative test result also could help doctors rule out Alzheimer’s in patients whose impairments may be related to some other health issue, disease or medication.”

Washington University School of Medicine in St. Louis is launching an international clinical trial aimed at preventing Alzheimer’s disease in people genetically destined to develop the illness at a young age. Unlike most other Alzheimer’s prevention trials, this one will enroll people before the disease has taken hold – up to 25 years before the expected onset of dementia.

Called the Primary Prevention Trial, the new study will investigate whether gantenerumab — an investigational antibody under development for Alzheimer’s disease by Roche and Genentech, a member of the Roche Group — can clear a key Alzheimer’s protein called amyloid beta, and slow or stop the disease. Amyloid is the chief component of plaques that dot the brains of people with the disease. Many scientists suspect the disease originates from the buildup of amyloid plaques in the brain that start to develop up to two decades before symptoms of dementia begin.

“Overwhelming evidence suggests that the most effective way to slow or stop amyloid beta is to prevent it from building up in the first place, but most of the drugs targeted to this protein have been tested in people who already have at least some early signs of the disease, such as memory loss – when the disease is far enough along that reducing amyloid alone isn’t likely to stop it,” said Eric McDade, DO, an associate professor of neurology and the trial’s principal investigator. “We’ll be recruiting participants as young as 18. In many ways, this trial will be a necessary test of the amyloid hypothesis, which has had a major influence on Alzheimer’s research and drug development over the past 30 years.”

The new trial involves families with rare genetic mutations that cause Alzheimer’s at a young age – typically in a person’s 50s, 40s or even 30s. A parent with such a mutation has a 50% chance of passing the genetic mutation to a child, and any child who inherits the mutation is all but guaranteed to develop symptoms of dementia near the same age as his or her parent. This certainty gives researchers an opportunity to evaluate the effectiveness of drugs designed to prevent Alzheimer’s.

“It’s exciting to think of the valuable insights this groundbreaking trial will provide in the prevention of Alzheimer’s dementia,” said Fred Miller, GHR Foundation’s chief operating officer and Alzheimer’s program lead. “We’re pleased to partner boldly on the multiple DIAN-TU trials, all made possible by the strong collaboration between academic researchers, government, industry, philanthropy and the DIAN families themselves.”​

Read more.