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

INTRODUCTION: The 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.

METHODS: The National Institute on Aging-Alzheimer's Association Framework is considered as it applies to clinical trials.

RESULTS: Using 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+.

DISCUSSION: The 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.