The PrecivityAD2 blood test by C2N Diagnostics is making significant strides in enhancing the accuracy and efficiency of Alzheimer's disease (AD) diagnosis and treatment decisions. This multianalyte assay, designed for patients 55 and older experiencing mild cognitive impairment (MCI) or dementia, utilizes high-resolution Liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify amyloid-β (Aβ)42 and Aβ40 isoforms, along with phosphorylated/non-phosphorylated tau217 peptides.
Enhanced Diagnostic Accuracy
The measurements obtained from the PrecivityAD2 test are combined to generate the Amyloid Probability Score 2 (APS2), a numerical score ranging from 0 to 100. An APS2 score of 48 or higher indicates the presence of brain amyloid plaques associated with AD pathology. Clinical validation in the PARIS (IDEAS sub-study; NCT02420756) and 11 MissionAD studies (NCT02956486 and NCT03036280) demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.94 and an accuracy of 88% when compared to amyloid PET scans.
In a large-scale study involving over 1200 patients in Sweden (NCT06122415 and NCT06120361), the test maintained a diagnostic accuracy of 90%, showing high concordance with cerebrospinal fluid analysis (AUC, 0.96-0.97). Notably, the test's performance remained consistent across various healthcare settings, including primary and secondary care, and was not affected by common comorbidities such as cardiovascular disease, chronic kidney disease, and diabetes.
Impact on Clinical Decision-Making
According to research findings, the clinical integration of blood biomarkers like PrecivityAD2 holds promise for enabling early detection and timely intervention in AD. A study published in Diagnostics highlighted that the use of a scalable, accessible, acceptable, and equitable blood biomarker test addresses an unmet need in diagnostic testing.
Mark Monane, MD, MBA, senior medical advisor at C2N Diagnostics, and colleagues conducted a prospective cohort study involving 203 individuals (median age, 74 years; 53% women) displaying signs of MCI or dementia consistent with AD. The study assessed the impact of the PrecivityAD2 test on clinical decision-making. The primary outcome focused on patient selection based on concordance between clinician-ordered tests and PrecivityAD2 utilization, as well as APS2 score interpretation by clinicians.
The study revealed a 99% clinical concordance with the PrecivityAD2 test (200 of 203 tests). Furthermore, patients with a positive APS2 result experienced a 35% increase in prescriptions for AD-related medications. From pre- to post-biomarker testing analysis, the mean clinician-reported AD probability decreased from 53% to 11% among patients with negative results and increased from 65% to 93% for patients testing positive.
Expert Perspectives
At the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, Joel B. Braunstein, MD, CEO of C2N Diagnostics, discussed how the PrecivityAD2 blood test enhances diagnostic accuracy for AD. "With the PrecivityAD2 test, clinicians’ diagnostic confidence in Alzheimer disease rose from around 50-60% to over 90%, guiding treatment decisions and reducing unnecessary testing," Braunstein noted.
Robert M. Carlile, MD, a neurology specialist at Palmetto Primary Care Physicians, emphasized the clinical significance of these findings. "The overall outcome has been clinically meaningful changes in decision-making around AD diagnostic certainty, drug therapy management, and additional brain amyloid evaluation among patients evaluated for cognitive impairment," Carlile stated. "This all increases our ability to develop diagnostic certainty and impact clinical management in patients."
