ATN Profile

The ATN framework provides an objective approach to determine the status of biological changes that are indicative of Alzheimer’s disease (AD). Overall, the ATN framework for blood-based biomarkers can complement imaging and CSF analysis and create an opportunity for a more effective patient journey. The ATN Profile test employs biomarkers that have been well-studied in clinical research:

A: Plasma Aβ42/40 immunoassay based on Sysmex reagents and technology. In general, Aβ42 proteins are known to have a high adhesion index and are typically referred to as “sticky,” thus complicating their assessment in blood or CSF samples. New technologies—including low binding tubes and high sensitivity immunoassay platforms that can detect down to picogram levels—have enabled better assessments. Ovod et al demonstrated that accurate amyloid beta assessments for AD from blood were possible using mass spectrometry techniques.¹ More recently, studies using Sysmex-based technology showed that plasma Aβ42/40 assessments could achieve levels similar to mass spectrometry-based methods for detecting AD pathology.^2,3

T: Plasma pTau-181 immunoassay based on Roche reagents and technology. Karikari et al showed the diagnostic utility of plasma pTau-181 in AD⁴ and additional studies that same year demonstrated that plasma pTau-181 correlates with tau PET,^5,6 thereby validating it as an important and useful BBM for AD pathology determination. Subsequent studies have demonstrated the prognostic value of combining Aβ42/40 testing with plasma pTau-181 on a Roche platform.⁷

N: Plasma NfL immunoassay based on Roche reagents and technology. NfL is an indicator of neurodegeneration but is not specific to any particular disease, as neurofilaments in blood are simply the result of axonal damage, regardless of cause. In CSF, total Tau is a key biomarker for neurodegeneration. However, for a complete blood-based solution, NfL is the more suitable biomarker⁸ for determining neurodegenerative disease staging.^9,10 The new updated draft guidelines do demote NfL from a core biomarker to a secondary one. Labcorp has chosen to leave the marker in the profile for clinical purposes since, even in the setting of normal beta-amyloid results, a raised NfL result may help alert the clinician to another non-Alzheimer’s condition.