Treatment‐related amyloid clearance (TRAC): a framework to characterize patients in the era of anti‐amyloid therapies

Abstract

Following regulatory approval of anti-amyloid beta (Aβ) therapies, a better characterization of patients receiving these treatments is needed to guide clinical management and inclusion in future trials. This Alzheimer's Association-convened workgroup proposes a terminology, treatment-related amyloid clearance (TRAC), to reflect alterations in disease pathophysiology based on biomarker evidence for clearance of Aβ deposits. TRAC designates biomarker-defined pharmacodynamic changes, rather than direct neuropathological evidence, and applies to individuals with (1) pretreatment biomarker confirmation of cerebral Aβ deposition, (2) treatment with an Aβ-targeting therapy, and (3) a follow-up biomarker test indicative of partial or full clearance of Aβ deposits. The workgroup currently recommends defining TRAC using amyloid-positron emission tomography (PET) and emphasizes the role of quantitative measurements for defining the degree of clearance. This framework is expected to be adapted over time in response to rapidly evolving biomarker and clinical advances and with the accumulation of real-world data on patients receiving anti-Aβ therapies. Highlights TRAC identifies patients with biomarker evidence for clearance of amyloid deposits. TRAC is currently defined using amyloid-PET. Full TRAC means that PET levels dropped below predetermined positivity threshold. Partial TRAC means that PET levels dropped significantly but remain above threshold. This framework is meant to guide future research on patients receiving treatment.