The National Institute on Aging—Alzheimer's Association Framework on Alzheimer's disease: Application to clinical trials

Abstract

IntroductionThe National Institute on Aging—Alzheimer's Association Research Framework on Alzheimer's disease (AD) represents an important advance in the biological characterization of the AD spectrum. MethodsThe National Institute on Aging—Alzheimer's Association Framework is considered as it applies to clinical trials. ResultsUsing the combination of amyloid (A), tau (T), and neurodegeneration (N) biomarkers, the Framework provides a means of defining the state of patients with regard to Alzheimer pathologic change. The Framework is relevant to clinical trials of disease-modifying agents, allowing participants to be characterized biologically at baseline. The ATN Framework can also inform trial outcomes. The preclinical phase of the disease after amyloid deposition is defined by A+T−N−, and the transition to prodromal disease and dementia is characterized by the addition of T and N. Most symptomatic patients in clinical trials are in the class of A+T+N− and A+T+N+. DiscussionThe National Institute on Aging—Alzheimer's Association Framework on AD represents progress in providing biomarker profiles of participants in the AD spectrum that can be used to help design clinical trials.