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

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

doi:10.1016/S1474-4422(12)70291-0

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

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

Research output: Contribution to journal › Comment/debate › peer-review

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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 language	English (US)
Pages (from-to)	207-216
Number of pages	10
Journal	The Lancet Neurology
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/S1474-4422(12)70291-0
State	Published - Feb 2013

ASJC Scopus subject areas

Clinical Neurology

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Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., 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

Jack, CR , Knopman, DS, Jagust, WJ, Petersen, RC, Weiner, MW, Aisen, PS, Shaw, LM, Vemuri, P, Wiste, HJ, Weigand, SD, Lesnick, TG, Pankratz, VS, Donohue, MC & Trojanowski, JQ 2013, 'Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers', The Lancet Neurology, vol. 12, no. 2, pp. 207-216. https://doi.org/10.1016/S1474-4422(12)70291-0

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

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.",

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

note = "Funding Information: We have received funding from the National Institutes of Health , grant AG11378 .",

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doi = "10.1016/S1474-4422(12)70291-0",

language = "English (US)",

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AU - Jack, Clifford R.

AU - Knopman, David S.

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AU - Petersen, Ronald C.

AU - Weiner, Michael W.

AU - Aisen, Paul S.

AU - Shaw, Leslie M.

AU - Vemuri, Prashanthi

AU - Wiste, Heather J.

AU - Weigand, Stephen D.

AU - Lesnick, Timothy G.

AU - Pankratz, Vernon S.

AU - Donohue, Michael C.

AU - Trojanowski, John Q.

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

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