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.
authors: Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA. jack.clifford@mayo.edu
authors: Clifford R
authors: CR
authors: Jack
authors: David S
authors: DS
authors: Knopman
authors: William J
authors: WJ
authors: Jagust
authors: Ronald C
authors: RC
authors: Petersen
authors: Michael W
authors: MW
authors: Weiner
authors: Paul S
authors: PS
authors: Aisen
authors: Leslie M
authors: LM
authors: Shaw
authors: Prashanthi
authors: P
authors: Vemuri
authors: Heather J
authors: HJ
authors: Wiste
authors: Stephen D
authors: SD
authors: Weigand
authors: Timothy G
authors: TG
authors: Lesnick
authors: Vernon S
authors: VS
authors: Pankratz
authors: Michael C
authors: MC
authors: Donohue
authors: John Q
authors: JQ
authors: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000209:etiology; D006801:Humans; D008954:Models, Biological; D017711:Nonlinear Dynamics; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins