Developing the ATX(N) classification for use across the Alzheimer disease continuum

Harald Hampel, Jeffrey Cummings, Kaj Blennow, Peng Gao, Clifford R. Jack, Andrea Vergallo

Research output: Contribution to journalReview articlepeer-review


Breakthroughs in the development of highly accurate fluid and neuroimaging biomarkers have catalysed the conceptual transformation of Alzheimer disease (AD) from the traditional clinical symptom-based definition to a clinical–biological construct along a temporal continuum. The AT(N) system is a symptom-agnostic classification scheme that categorizes individuals using biomarkers that chart core AD pathophysiological features, namely the amyloid-β (Aβ) pathway (A), tau-mediated pathophysiology (T) and neurodegeneration (N). This biomarker matrix is now expanding towards an ATX(N) system, where X represents novel candidate biomarkers for additional pathophysiological mechanisms such as neuroimmune dysregulation, synaptic dysfunction and blood–brain barrier alterations. In this Perspective, we describe the conceptual framework and clinical importance of the existing AT(N) system and the evolving ATX(N) system. We provide a state-of-the-art summary of the potential contexts of use of these systems in AD clinical trials and future clinical practice. We also discuss current challenges related to the validation, standardization and qualification process and provide an outlook on the real-world application of the AT(N) system.

Original languageEnglish (US)
Pages (from-to)580-589
Number of pages10
JournalNature Reviews Neurology
Issue number9
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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