FDA Clears Blood Test Designed to Detect Alzheimer’s-Linked Amyloid Pathology
A blood test developed from technology pioneered at Washington University School of Medicine in St. Louis has received clearance from the U.S. Food and Drug Administration to be marketed as an aid in evaluating Alzheimer’s disease. Known as PrecivityAD2, the test was developed and validated by C2N Diagnostics, a WashU startup co-founded by neurologists Randall J. Bateman and David M. Holtzman. Its clearance marks a significant step in the movement of Alzheimer’s diagnostics away from procedures that require spinal fluid or specialized brain imaging and toward blood-based testing that can be incorporated more easily into routine clinical care. The test is intended for use in certain patients with cognitive symptoms and is designed to identify biological evidence associated with Alzheimer’s disease, rather than determine a diagnosis independently of a physician’s assessment.
PrecivityAD2 detects the molecular signature of amyloid pathology by measuring several proteins in a blood sample. Alzheimer’s disease is characterized by the accumulation of amyloid plaques and abnormal tau proteins in the brain, biological changes that can begin years before dementia becomes apparent. The test quantifies the ratio of two amyloid-beta molecules, Aβ42 and Aβ40, together with two tau-related biomarkers, phosphorylated tau217 and total tau217. The relative abundance of these molecules provides information about whether amyloid pathology is likely to be present. In particular, a reduced Aβ42-to-Aβ40 ratio is associated with amyloid deposition, while elevations in phosphorylated and total tau can reflect downstream changes linked to neurodegeneration. By combining these measurements, PrecivityAD2 generates a composite result intended to support clinical evaluation.
Unlike many blood tests that rely on antibody-based immunoassays, PrecivityAD2 uses high-resolution mass spectrometry. This analytical approach separates molecules according to their mass and chemical properties, allowing researchers to distinguish closely related protein fragments and to measure them quantitatively. That distinction is especially important for amyloid-beta and tau, which exist in multiple molecular forms that may differ by only a small structural feature. Mass spectrometry can target these specific molecular species with high analytical precision, reducing the risk that similar proteins or fragments will be mistaken for the biomarkers of interest. The method also enables simultaneous examination of several Alzheimer’s-associated signals in a single blood draw, creating a biochemical profile rather than relying on one marker alone.
The availability of such a test could change how clinicians investigate memory loss and other cognitive symptoms. Current biological confirmation of Alzheimer’s pathology may involve cerebrospinal fluid collected through a lumbar puncture or positron emission tomography scans that use radioactive tracers to visualize amyloid in the brain. Both approaches can be highly informative, but they may be expensive, time-consuming, invasive or unavailable in many clinical settings. A blood test can be collected in an ordinary medical laboratory and may make biomarker assessment accessible to a substantially larger number of patients. However, the result is not intended to replace a complete neurological evaluation. Physicians must interpret it alongside a patient’s symptoms, medical history, cognitive testing, examination findings and, when necessary, imaging or cerebrospinal fluid data.
Studies reported by WashU and C2N have found that PrecivityAD2 can identify Alzheimer’s-related amyloid pathology with more than 90% accuracy in evaluated patient groups. The test has shown performance comparable to established cerebrospinal fluid measurements and amyloid brain scans, including among people with mild cognitive symptoms. Such results are important because early symptomatic patients often occupy a diagnostic gray zone: their memory or thinking problems may be subtle, yet the underlying disease process may already be advancing. A reliable blood biomarker could help separate patients who are likely to have amyloid pathology from those whose symptoms arise from another condition. At the same time, accuracy is not absolute, and a positive or negative result may require confirmation when it conflicts with the broader clinical picture.
The timing of the FDA clearance is particularly consequential because the first treatments capable of slowing the progression of Alzheimer’s disease have recently become available. These therapies are designed for patients with confirmed amyloid pathology and are generally more useful when introduced earlier in the course of disease, before extensive neuronal damage has occurred. A faster route to biological assessment could help eligible patients and their physicians consider treatment sooner, while also preventing people without amyloid pathology from receiving therapies that are unlikely to benefit them. Earlier information may additionally support planning for follow-up care, clinical trial participation and management of other medical conditions that can worsen cognitive performance. The test therefore has potential value not only as a diagnostic tool but also as part of a broader treatment decision-making process.
The scientific foundation for PrecivityAD2 emerged from research conducted in the laboratories of Bateman and Holtzman at WashU Medicine. Their work investigated how amyloid-beta and tau are produced, transported and cleared in the brain and cerebrospinal fluid. They helped pioneer stable isotope-linked kinetics, or SILK, a technique that uses labeled molecules to track the production and removal of proteins in living people. By measuring how quickly amyloid-beta is generated and cleared, researchers gained a more detailed view of the biological processes that precede plaque formation. This research provided a framework for developing sensitive assays capable of detecting disease-related changes in blood, where Alzheimer’s biomarkers are present at far lower concentrations than in cerebrospinal fluid.
Bateman, Holtzman and colleagues worked with WashU’s Office of Technology Management to patent components of the technology and co-founded C2N Diagnostics in 2007 to pursue commercial development. C2N obtained exclusive commercial licenses to relevant inventions from the university and refined the assays for clinical use. The company’s work illustrates how discoveries made in academic laboratories can move through intellectual property development, analytical validation and regulatory review before reaching physicians. C2N now employs more than 120 researchers, physicians and other professionals and is expanding its headquarters in St. Louis’ Cortex Innovation District. The continuing research relationship between WashU Medicine and C2N has helped advance the test from an experimental measurement of Alzheimer’s biology to a regulated product intended for use in healthcare systems.
FDA clearance means that the agency reviewed evidence supporting the test’s analytical and clinical performance and determined that it could be marketed for its specified use. It does not mean that PrecivityAD2 can diagnose every case of Alzheimer’s disease, detect all causes of cognitive decline or replace professional judgment. The result identifies the likelihood of amyloid plaques associated with Alzheimer’s pathology, while the patient’s symptoms and other findings remain essential to determining whether Alzheimer’s disease is the cause of impairment. Broader marketing may nevertheless encourage adoption by clinicians and health systems that require regulatory authorization before incorporating a diagnostic into practice. It may also help insurers evaluate coverage, potentially reducing financial barriers to testing. As blood biomarkers become more sophisticated, PrecivityAD2 could help establish a new diagnostic pathway in which Alzheimer’s biology is assessed earlier, more conveniently and at a scale that was previously difficult to achieve.
Subject of Research: Blood-based diagnosis and biomarker detection for Alzheimer’s disease.
Article Title: FDA Clears Blood Test Designed to Detect Alzheimer’s-Linked Amyloid Pathology
Web References: https://medicine.washu.edu/news/alzheimers-blood-test-performs-as-well-as-fda-approved-spinal-fluid-tests/ ; https://neurology.wustl.edu/people/randall-bateman-md/ ; https://holtzmanlab.wustl.edu/people/david-m-holtzman-md/ ; https://medicine.washu.edu/
References: Washington University School of Medicine in St. Louis; C2N Diagnostics; U.S. Food and Drug Administration.
Image Credits: Matt Miller/WashU Medicine.
Keywords: Alzheimer’s disease, PrecivityAD2, blood test, amyloid beta, tau protein, p-tau217, mass spectrometry, biomarkers, neurology, dementia, early diagnosis, C2N Diagnostics, Washington University School of Medicine.
