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Neurology. 2016 Aug 2;87(5):539-47. doi: 10.1212/WNL.0000000000002923. Epub 2016 Jul 1.

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

Author information

1
From the Departments of Radiology (C.R.J.) and Neurology (D.S.K., R.C.P.), Mayo Clinic, Rochester, MN; Rush Alzheimer's Disease Center (D.A.B.), Rush University Medical Center, Chicago, IL; Clinical Neurochemistry Lab (K.B.), Department of Neuroscience and Physiology, University of Gothenburg, Mölndal Hospital, Sahlgrenska University Hospital, Mölndal, Sweden; Alzheimer's Association (M.C.C.), Chicago, IL; Division of Neurology (H.H.F.), UBC Hospital Clinic for Alzheimer's Disease and Related Disorders, University of British Columbia, Vancouver, Canada; Memory Clinic (G.B.F.), University Hospitals and University of Geneva, Switzerland; IRCCS Fatebenefratelli (G.B.F.), The National Centre for Alzheimer's Disease, Brescia, Italy; Sorbonne Universités (H.H.), Université Pierre et Marie Curie, Paris; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) and Institut du Cerveau et de la Moelle épinière (ICM) (H.H.), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; Departments of Radiology and Neurology (K.A.J.), Massachusetts General Hospital, Harvard Medical School, Boston; Alzheimer Center and Department of Neurology (P.S.), Vrije Universiteit Amsterdam, the Netherlands; Center for Alzheimer Research and Treatment (R.A.S.), Brigham and Women's Hospital and Massachusetts General Hospital, Harvard Medical School, Boston; Centre des Maladies Cognitives et Comportementales (B.D.), Institut du Cerveau et de la Moelle épinière, Paris; and Université Pierre et Marie Curie-Paris 6 (B.D.), AP-HP, Hôpital de la Salpêtrière, Paris, France. jack.clifford@mayo.edu.
2
From the Departments of Radiology (C.R.J.) and Neurology (D.S.K., R.C.P.), Mayo Clinic, Rochester, MN; Rush Alzheimer's Disease Center (D.A.B.), Rush University Medical Center, Chicago, IL; Clinical Neurochemistry Lab (K.B.), Department of Neuroscience and Physiology, University of Gothenburg, Mölndal Hospital, Sahlgrenska University Hospital, Mölndal, Sweden; Alzheimer's Association (M.C.C.), Chicago, IL; Division of Neurology (H.H.F.), UBC Hospital Clinic for Alzheimer's Disease and Related Disorders, University of British Columbia, Vancouver, Canada; Memory Clinic (G.B.F.), University Hospitals and University of Geneva, Switzerland; IRCCS Fatebenefratelli (G.B.F.), The National Centre for Alzheimer's Disease, Brescia, Italy; Sorbonne Universités (H.H.), Université Pierre et Marie Curie, Paris; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) and Institut du Cerveau et de la Moelle épinière (ICM) (H.H.), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France; Helen Wills Neuroscience Institute (W.J.J.), University of California, Berkeley; Departments of Radiology and Neurology (K.A.J.), Massachusetts General Hospital, Harvard Medical School, Boston; Alzheimer Center and Department of Neurology (P.S.), Vrije Universiteit Amsterdam, the Netherlands; Center for Alzheimer Research and Treatment (R.A.S.), Brigham and Women's Hospital and Massachusetts General Hospital, Harvard Medical School, Boston; Centre des Maladies Cognitives et Comportementales (B.D.), Institut du Cerveau et de la Moelle épinière, Paris; and Université Pierre et Marie Curie-Paris 6 (B.D.), AP-HP, Hôpital de la Salpêtrière, Paris, France.

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.

PMID:
27371494
PMCID:
PMC4970664
DOI:
10.1212/WNL.0000000000002923
[Indexed for MEDLINE]
Free PMC Article

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