There’s good news for people who are concerned about Alzheimer’s disease (AD). Individuals experiencing symptoms of dementia can now be evaluated using a blood sample drawn at a physician’s office, without the need for expensive and invasive diagnostic testing. The screening test is expected to boost early diagnosis and treatment for AD, and was developed in part thanks to BrightFocus Foundation and its generous Alzheimer’s Disease Research donors, who provided support for the effort from early stages.
In late 2020, the PrecivityAD™ blood test, developed by C₂N Diagnostics, became commercially available for use in routine clinical care. PrecivityAD consistently detects the presence or absence of brain amyloid (Aβ) plaques with an accuracy of 86% when confirmed by amyloid PET scans. The PrecivityAD™ test relies on a single blood draw and combines the blood ratio of amyloid-beta (Aß) proteins (specifically Aβ42/40) with a person’s age and APOE genotype to determine an amyloid positivity score. The amyloid positivity score can then be used to determine the likelihood of Alzheimer’s and what additional testing and follow-up may be needed.
Compared with other current diagnostic methods, including PET imaging and cerebrospinal fluid (CSF) analysis, results using the PrecivityAD test can be obtained in a fraction of the time and expense. A blood sample collected in a single office visit is sent to C₂N Diagnostics’ clinical laboratory for analysis. After processing and analysis, C₂N sends the physician a report containing their patient’s results, along with guidance for interpretation. The company is providing one-on-one support to office-based physicians who are using PrecivityAD to help diagnose patients.
It must be emphasized that Alzheimer’s is not a normal part of growing older. Yet currently in the United States, studies have shown that only about half of all people who have Alzheimer’s receive a clinical diagnosis.
The underdiagnosis of AD deprives people of the opportunity to understand and manage their AD effectively. It also robs them and their families of valuable time to become more informed, plan, and make decisions about what’s ahead. At the same time, a misdiagnosis of Alzheimer’s, when another condition is responsible for the dementia, may delay an individual from receiving timely and proper care that can improve or even reverse the cause of the symptoms.
Early diagnosis is important because lifestyle interventions for Alzheimer’s – things like sleep, exercise, and dietary changes – work best at early stages of the disease. Evidence has shown that many drugs and therapies now in development for Alzheimer’s work best at the early stages; in fact, the earlier, the better. Many therapies are being targeted to the early and (in some cases) preclinical stages of Alzheimer’s, before classic symptoms like memory loss and behavior change are noticeable.
Currently, many primary care physicians use cognitive screening tests to identify problems that might be indicative of AD or another cause of dementia. However, until now it’s been somewhat of a guessing game for patients whose results are inconclusive, particularly if no other causes for their cognitive impairment can be found.
Hoping to provide more certainty, the medical community has awaited the arrival of a relatively simple Alzheimer’s blood test that could serve as an early warning and/or diagnosis for such patients. In addition, an Alzheimer’s blood test has been sought by the research community as a way to speed up clinical trial recruitment and the effort to develop cures. Currently, following recruitment, most trial volunteers undergo costly and time-consuming imaging and/or CSF testing to confirm their diagnosis – and ultimately only about 20 percent of them are found to actually have amyloid beta plaques in their brains. The PrecivityAD test – and eventually others like it – can be used as a screening tool for enrollment.
Because the PrecivityAD test is expected to boost diagnosis, and at earlier stages, it is considered a recent top breakthrough in the Alzheimer’s field. The result of decades of scientific research and testing, it is the first blood-based Alzheimer’s test to come to market, although there are several others now in development.
Just this month, Molecular Neurodegeneration, a peer-reviewed journal supported by BrightFocus, published data on the effectiveness of the PrecivityAD blood test. The authors acknowledge BrightFocus support for their research, and state that the test’s “excellent performance” for Alzheimer’s disease (AD) diagnosis allows for “improved medical decision making and management, streamlined AD clinical trial enrollment, and better identification of who may benefit from an AD specific therapy.”
C₂N Diagnostics says that forthcoming published research will further increase understanding of the test’s analytical performance and clinical robustness.
BrightFocus Role in the Development of the PrecivityAD Test
BrightFocus and its donors played a key role in the discovery and development of the PrecivityAD test, beginning with Randall Bateman, MD, a name well known in Alzheimer’s research circles. He is the Charles F. and Joanne Knight Distinguished Professor of Neurology at the Washington University School of Medicine in St. Louis, and he also directs the Dominantly Inherited Alzheimer Network (DIAN) study and its clinical study arm, the DIAN Trials Unit.
DIAN is a long-running federally-funded effort to “decode” the genetic causes of inherited forms of Alzheimer’s. Dominantly inherited forms represent only a fraction of all AD, less than one percent, and yet studying them has informed much of what we know about the more prevalent forms of late-onset Alzheimer’s that occurs later in life. Late-onset AD is influenced by multiple risk factors, including (in part) a person’s genes, race, and innate biology, but also health, behavior, environment, education, and more.
Early in his career, Dr. Bateman was among a small group of visionaries who sought to integrate knowledge and research findings about early-onset, inherited forms with late-onset AD. In 2008, he was awarded a BrightFocus Alzheimer’s Disease Research (ADR) grant to find answers to a foundational question that affects both types, which is how APOE status drives AD risk. APOE genotype continues to be regarded as one of the chief genetic risk factors behind late-onset forms, and is one of the factors analyzed in the PrecivityAD blood test.
Dr. Bateman collaborated with his mentor, another ADR grantee at Washington University School of Medicine, and a leader in the field of Alzheimer’s research: David Holtzman, MD. Dr. Holtzman is now chief of neurology there and chairman of the BrightFocus ADR Scientific Review Committee.
In 2007, in an effort to put all that they and others were learning about AD into action, the two researchers teamed up with several biotech entrepreneurs – Joel Braunstein, MD, MBA and Ilana Fogelman, MD, MPH from LifeTech Research, Inc, out of Baltimore, Maryland – to form C₂N Diagnostics, LLC. C₂N is a privately held protein diagnostic and therapeutic discovery company targeting progressive neurodegeneration. The company is based in St. Louis’ small but powerful biotech corridor, at the Center for Emerging Technologies. Dr. Braunstein is president and CEO of C₂N, and Dr. Fogelman is the vice president of Regulatory and Clinical Affairs.
Meanwhile, at their university labs, the research teams of Holtzman and Bateman continued to pursue questions that might ultimately translate into “real life” solutions for Alzheimer’s. Fast forward to 2014 and 2017, when Dr. Bateman received new ADR grants to pioneer techniques for measuring and tracking tau deposits and amyloid plaque growth, respectively, in the human brain. These grants helped refine techniques for detecting and measuring AD-related proteins in blood and became the scientific underpinning for the PrecivityAD test.
As positive results came in from the projects, BrightFocus further invested, supporting C₂N’s efforts to commercially develop the PrecivityAD test, in 2016 awarding a $750,000 ADR grant to C₂N scientists Philip Verghese, PhD (now C₂N’s director of Research and Development) and Dr. Braunstein. Prior to that, Dr. Verghese received an ADR postdoctoral fellowship grant for a project focused on how APOE genetic variants affect amyloid-beta production and aggregation.
Success came late last year, following a highly focused effort by C₂N’s product developers, when the PrecivityAD test became commercially available under the Clinical Laboratory Improvement Amendments (CLIA) regulations as a clinical laboratory test in 48 states and Puerto Rico. (The two current exceptions are Maryland and New York, which have separate certification requirements for clinical labs; these certifications are expected to be obtained in the near future.) One month after the U.S. launch, C₂N obtained a marketing authorization (known as a CE Mark) to sell the PrecivityAD™ test in various member countries within the European Union.
Now, thanks in part to the unwavering support of BrightFocus and its donors, Dr. Bateman’s early vision – that it might be possible to measure Alzheimer’s-related proteins in blood – became a reality in the form of the PrecivityAD blood test, the first Alzheimer’s blood test to reach the market.
Recently Dr. Bateman expressed gratitude for the long and successful relationship he’s forged with BrightFocus and its ADR program.
“Taking an idea, or a hypothesis, to the point where it has an impact on a disease is a long journey,” Dr. Bateman said, “yet the rewards – in terms of earlier diagnosis and accelerating cures – were so substantial, we were invigorated to press on[MT1] .
“I appreciate BrightFocus for supporting my early discoveries, and for recognizing that this work would translate into real-world benefits,” he said.
“It’s taken a lot of teamwork to get to this point, and we are grateful to BrightFocus and its donors for believing in our efforts.”
- A Blood Sample Speeds Alzheimer’s Diagnosis (BrightFocus Research in Brief, 2021)
- The PrecivityAD™ Alzheimer’s Test: A Q&A with C2N’s Joel Braunstein, PhD
- Encouraging Sign for Alzheimer’s Blood Test in BrightFocus-Funded Study (BrightFocus Press Release, 2019)
- BrightFocus-funded Alzheimer’s Test Gets Encouraging Sign from FDA (Science News story, 2019)
- Science News feature on Bateman team’s pioneering research behind PrecivityADAD blood test (2018)
- Randall Bateman 2017-21 ADR Grant from BrightFocus
- Phillip Verghese and Joel Braunstein 2016-18 ADR Grant from BrightFocus
- Randall Bateman 2014-17 ADR Grant from BrightFocus
- Randall Bateman 2008-10 ADR Grant from BrightFocus
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