First Widely Accessible Alzheimer Disease Blood Test Reaches Clinic

Howard Fillit, MD

C2N Diagnostics announced that its PrecivityAD blood test, a non-invasive blood test that correctly predicts Alzheimer disease (AD) brain pathology in people with memory and thinking issues, has arrived into the clinic setting.¹

The PrecivityAD test identifies whether a patient is likely to have amyloid plaques in the brain. It relies on precise and robust quantitation of the amyloid-beta 42/40 ratio (Aß 42/40) and detection of the Apoliproprotein E proteotype (equivalent to APOE genotype) in blood samples, using C2N’s proprietary mass spectrometry platform.

The test is currently available in 45 states, the District of Columbia, and Puerto Rico, and is only available through an order by a physician. Additionally, it is not currently covered by private insurance payers, Medicare or Medicaid. Patients are responsible for paying out-of-pocket for the test.² Funding provided by the Alzheimer’s Drug Discovery Foundation (ADDF), including $2.8 million over the last decade and $2.2 million to accelerate clinical validation and accreditation, has helped the test reach this point.³

“This is really an importance advance. You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” Howard Fillit, MD, founding executive director and chief science officer, ADDF, said in a statement. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”

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The PrecivityAD blood test’s validity was analyzed in blood samples from 686 patients with cognitive impairment and a clinical suspicion of AD. All 686 patients underwent amyloid PET imaging with an FDA-approved amyloid tracer. Based on the data, the test correctly identified brain amyloid plaque status in 86% of the patients.²

The Receiver Operating Characteristic (ROC) for the analysis had an area under the curve (AUC) of 0.88. At the lower score cut point, the positive percent agreement (sensitivity) was 92%. At the higher score cut point, the negative percent agreement (specificity) was 77%. Among them, 55% (n = 378) were amyloid positive by amyloid PET scan.

The test involves a 3-step process. First, a health care provider orders the PrecivityAD blood test and schedules a blood draw appointment. Blood samples taken from the test are sent to a specialized laboratory facility and are automated, which allows for C2N to process samples in a routine and repeatable manner. From there, C2N sends the physician the patient’s lab report, which details the levels of biomarkers and provides an overall combined score, known as the Amyloid Probability Score (APS), to access the likelihood of amyloid plaques in the brain.

Low APS scores between 0–36 are consistent with a negative amyloid positron emission tomography (PET) scan result and, thus, a low likelihood of amyloid plaques. These scores may be inconsistent with AD diagnosis but could indicate other causes of cognitive symptoms. Intermediate APS scores between 37–57 do not distinguish the presence or absence of amyloid plaques and also indicates that further diagnostic evaluation may be needed to assess underlying causes for a patient’s cognitive symptoms.

A high APS score (58–100) is consistent with a positive amyloid PET scan result and indicates a high likelihood of amyloid plaques. The presence of amyloid plaques is consistent with AD but is not considered a final diagnosis.

“Our mission is to translate exceptional science into unique diagnostics that can help as many people as possible. The PrecivityAD blood test introduces a new option for patients, families and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, chief executive officer, C2N, said in a statement.

C2N also noted that it plans on moving ahead with the development of a Brain Health Panel that seeks to detect multiple blood-based markers for AD to aid in better disease staging, treatment monitoring, and differential diagnosis.

The ADDF initiated the Diagnostics Accelerator (DxA) in 2018—which mobilized commitments totaling $50 million—to fast-track the development of simple, cost-effective diagnostic tools and biomarkers, such as blood tests, eye scans and digital technologies.³ “There are several blood tests in development for beta-amyloid, as well as other targets that will further revolutionize the development of new drugs for Alzheimer’s disease the same way a blood test for cholesterol did for heart disease. With new biomarkers, precision medicine is possible,” Fillit added.

REFERENCES

1. Alzheimer’s breakthrough: C2N first to offer a widely accessible blood test. News release. C2N Diagnostics. October 29, 2020. Accessed November 5, 2020. https://precivityad.com/news/alzheimers-breakthrough​

2. The PrecivityAD blood test answers calls from patients, advocates, and physicians who want earlier answers. PrecivityAD. Accessed November 5, 2020. https://precivityad.com/physicians​

3. Breakthrough moment for Alzheimer’s disease: first blood test comes to clinic. News release. Alzheimer’s Drug Discover Foundation. October 29, 2020. Accessed November 5, 2020. https://www.alzdiscovery.org/news-room/announcements/breakthrough-moment-for-alzheimers-disease-first-blood-test-comes-to-clinic​