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

Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, et al.
Lancet Neurol. 2013 Feb; 12(2):207-16. PMID: 23332364. Abstract


Submitted by Wei Chen on



The model of Alzheimer’s disease (AD) biomarkers described the temporal evolution of AD biomarkers including Aβ, tau and structural or functional changes based FDG PET and MRI. The authors clarified that these biomarkers does not begin at the same time, and notprogress in parallel, which is important for us to further research of biomarkers of different AD stages.

Five AD biomarkers established in this article are sufficiently validated to have been incorporated into clinical diagnostic criteria and commonly used in therapeutic trials. 

The authors developped  a few years ago a very interesting model describing the temporal evolution of AD biomarkers  in  relation to each other and to the onset and progression of clinical symptoms. The authors identified the time line of the major AD biomarkers  when they become abnormal : CSF Aβ42 and amyloid PET are dynamic earliest followed by CSF tau and FDG PET, then structural MRI, followed by clinical symptoms. These sequences were further studied  and in this paper the authors evaluated temporal ordering of CSF biomarkers and structural MRI in 401 elderly cognitively normal (CN), MCI and AD dementia subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) improving the previous study.  The general temporal ordering framework of the model where amyloid biomarkers become abnormal first then biomarkers of neurodegeneration, followed by clinical symptoms. This study represent a mile stone to unravell the time line of disease.