Two Independent Research Studies Bolster Method That C₂N’s PrecivityAD™ Blood Test Uses to Aid Clinicians in Alzheimer’s Disease Diagnoses

Oct 28

The Journal of the American Medical Association Neurology published findings from BioFINDER’s large comparison of blood plasma amyloid-beta assays. One of the types of assays included in the study was the liquid chromatography–mass spectrometry (LC-MS/MS) assay that Dr. Bateman and his laboratory developed at Washington University School of Medicine that underpins the PrecivityAD™ blood test. The international research group found it performed the best out of seven amyloid assays as well as against the measurement of phosphorylated tau-217, another Alzheimer’s biomarker.

The JAMA Neurology piece also highlighted confirmation of the BioFINDER results based on blood samples analyzed from the Alzheimer Disease Neuroimaging Initiative (ADNI), an eminent longitudinal cohort study in North America that has been tracking patients since 2004.

The paper says that “plasma Aß42/40 quantified with the IP-MS-WashU approach showed significantly better performance than the immunoassays.” It adds that the “IP-MS blood test for Aß developed by Washington University can now be used in clinical care in US,” which is indeed occurring through C₂N’s PrecivityAD™ test.

Separately, a group of leading researchers presented their round-robin findings at the Alzheimer’s Association International Conference (AAIC) 2021 meeting held in Denver, CO, this past summer; they found that measuring amyloid beta (Aβ) in a patient’s blood can be a pre-screen or a substitute for costly PET scans or invasive cerebrospinal fluid (also known as spinal tap) screenings that clinicians use to diagnose Alzheimer’s disease. The researchers examined the performance of six plasma Aβ assays in their ability to identify Aβ as determined by PET scans; they found that the LC-MS/MS assay that Dr. Bateman developed performed best in its ability to identify amyloid plaque.

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Ask the Expert

Philip Verghese, Ph.D., C2N’s Director of Research, Development and Operations, is featured in this edition of Ask the Expert. Phillp says he enjoys being part of a team that developed the PrecivityAD™ blood test; it’s innovative, widely accessible, substantially less invasive, less costly and logistically simple to determine one of the key pathologic hallmark signs of Alzheimer’s disease.

Philip says, “We have put together a road map for how a small, innovative company can change the landscape of the clinical diagnosis for Alzheimer’s disease. This is very satisfying from an organizational point of view. I think the biggest challenge of creating a test for clinical use was how to navigate and balance the needs and expectations of different stakeholders — patients, clinical community, academic community, advocacy groups and regulators.”

Question to Philip: How does Apolipoprotein E (ApoE) serve as a genetic risk marker for Alzheimer’s disease and how is it part of the PrecivityAD™ blood test process?

Philip’s Answer: The Apolipoprotein E (ApoE) gene exists as three main forms — ApoE2, ApoE3 and ApoE4. Genetically, the ApoE4 form of the ApoE gene is the strongest risk factor for Alzheimer’s disease.

Individuals with one copy of ApoE4 have a threefold higher risk, while those who inherit two copies of ApoE4 have an eight to 12-fold greater risk of developing Alzheimer’s dementia compared to ApoE4 non-carriers. ApoE2 individuals have reduced risk for developing late-onset Alzheimer’s.

ApoE forms differentially influence the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain, the pathological hallmarks of Alzheimer’s disease. ApoE4 genotype is a significant risk factor for brain amyloid accumulation. It is important to note that ApoE4 is neither necessary nor sufficient for the development of Alzheimer’s disease so that ApoE genetic information alone cannot be used for the diagnosis of Alzheimer’s disease. A person’s overall risk for developing Alzheimer’s disease is dependent upon on many genetic, biochemical, epigenetic, and environmental factors.

The PrecivityAD™ test measures the concentrations of amyloid beta 42 and 40 (Aβ42 and Aβ40), as well as the presence of apolipoprotein E (ApoE) isoforms in the blood. The test indicates if an individual is likely to have amyloid plaques in the brain, a hallmark of Alzheimer’s disease. ApoE4 genotype is a significant risk factor for amyloid accumulation in the brain and Alzheimer’s disease, and its incorporation into C2N’s proprietary algorithm increases the accuracy of the test. Using data from 686 patients, an algorithm based on plasma Aβ42/40 ratio, ApoE genotype, and patient age improved the accuracy of the prediction between amyloid PET positive versus amyloid PET negative patients, as compared to using the Aβ42/40 ratio alone.

In the News

Science magazine, the peer-reviewed academic journal of the American Association for the Advancement of Science, recently covered PrecivityAD™ in a story about clinicians diagnosing Alzheimer’s disease. The article explained how the PrecivityAD™ blood test uses mass spectrometry, a highly precise technique, to quantify the blood ratio of amyloid beta 42 and 40 peptides (the Aβ42/Aβ40 ratio) and to characterize the patient’s Apolipoprotein E proteotype (equivalent to ApoE genotype) profile — a risk factor for Alzheimer’s disease.
Clinicians in Maryland and Pennsylvania are now able to offer the PrecvityAD™ blood test. Forty-nine states, the District of Columbia and Puerto Rico have all granted C2N Diagnostics a CLIA certificate to conduct such testing.
BrightFocus Foundation’s Alzheimer’s Day of Hope highlighted the amazing research BrightFocus funds to find a cure for Alzheimer's disease.BrightFocus is an early grant supporter of the PrecivityAD™ blood test. Learn about it on Youtube >
Best Startup named C₂N Diagnostics one of the “Best Missouri Biotechnology Companies and Startups.” Best Startup says it picks startups and companies that are “taking a variety of approaches to innovating the Biotechnology industry, but are all exceptional companies well worth a follow.” Read more here >
Alzheimer’s and Dementia: The Journal of the Alzheimer's Association included details about the National Institutes of Health’s National Institute on Aging (NIA) support of C₂N in developing PrecivityAD™. The paper explained the NIA Small Business Innovation Research grants and how PrecivityAD™ is “the first amyloid blood test to become available to doctors, who can send blood samples to C2N’s lab to analyze blood for amyloid.” Read the research paper >