A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers
2016/07/02 by Clifford R. Jack, David A. Bennett, Kaj Blennow +13 · 1,902 citations
Medicine · Neuroscience · Psychology · #Alzheimer's disease research and treatments #Bioinformatics #Biology #Biomarker #Dementia #Dementia and Cognitive Impairment Research #Disease #Genetics #Medicine #Neurodegeneration #Neurological Disease Mechanisms and Treatments #Oncology #Pathology #Population #Psychology
paper · pdf · doi:10.1212/wnl.0000000000002923
published in Neurology 87(5), 539-547 (Lippincott Williams & Wilkins)
openalex publication_date 2016/07/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Abstract
Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a β-amyloid biomarker (amyloid PET or CSF Aβ42); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([(18)F]-fluorodeoxyglucose-PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T-/N-, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme.
Citations
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