Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers

Clifford R Jr. Jack, David S Knopman, William J. Jagust, Ronald Carl Petersen, Michael W. Weiner, Paul S. Aisen, Leslie M. Shaw, Prashanthi D Vemuri, Heather J. Wiste, Stephen D. Weigand, Timothy G. Lesnick, Vernon S. Pankratz, Michael C. Donohue, John Q. Trojanowski

Research output: Contribution to journalArticle

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Abstract

In 2010, we put forward a hypothetical model of the major biomarkers of Alzheimer's disease (AD). The model was received with interest because we described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms. Since then, evidence has accumulated that supports the major assumptions of this model. Evidence has also appeared that challenges some of our assumptions, which has allowed us to modify our original model. Refinements to our model include indexing of individuals by time rather than clinical symptom severity; incorporation of interindividual variability in cognitive impairment associated with progression of AD pathophysiology; modifications of the specific temporal ordering of some biomarkers; and recognition that the two major proteinopathies underlying AD biomarker changes, amyloid β (Aβ) and tau, might be initiated independently in sporadic AD, in which we hypothesise that an incident Aβ pathophysiology can accelerate antecedent limbic and brainstem tauopathy.

Original languageEnglish (US)
Pages (from-to)207-216
Number of pages10
JournalThe Lancet Neurology
Volume12
Issue number2
DOIs
StatePublished - Feb 2013

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Jack, C. R. J., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P. D., Wiste, H. J., Weigand, S. D., Lesnick, T. G., Pankratz, V. S., Donohue, M. C., & Trojanowski, J. Q. (2013). Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers. The Lancet Neurology, 12(2), 207-216. https://doi.org/10.1016/S1474-4422(12)70291-0