A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers

By Clifford R. Jack Jr., David A. Bennett, Kaj Blennow, M. Carrillo, H. Feldman, Giovanni B. Frisoni, Harald Hampel, William J. Jagust, Keith A. Johnson, David S. Knopman and 4 more. Neurology, 2016

1,607 citations recorded by the source corpus.

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 ([18F]-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.

Subfields: Neurology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/cd9ccf982c82017b2a5e237b3a0f3332e2499e10

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Citations in the corpus

Religious Orders Study and Rush Memory and Aging Project (2018, methodology): “The framework is based largely on a recently proposed A/T/N classification scheme [368].”
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease (2018, positive): “The AT(N) system was designed with both a CSF and an imaging biomarker in each of the three biomarker groups (Table 1) [16].”
Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease (2017, methodology): “This further supports the argument that regions affected early by tau pathology such as entorhinal cortex should be incorporated into regional tau PET biomarkers (as done by Jack et al., 2016b).”
Understanding the impact of sex and gender in Alzheimer's disease: A call to action (2018, background): “[112] Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al.”
Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup (2024, neutral): “97,170,8 When all evidence is considered it is unclear how best to categorize this measure in the current document.”
Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group (2021, background): “…scheme to include AD for research purposes diagnosed at a preclinical stage of the disease, on the presence of both in-vivo amyloid and tau positivity “where the risk of a further progression to clinical AD is high” 7 , a proposal that was further developed by Jack and collaborators 1,8 .”