title: Biomarker modeling of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a slowly progressing disorder in which pathophysiological abnormalities, detectable in vivo by biomarkers, precede overt clinical symptoms by many years to decades. Five AD biomarkers are sufficiently validated to have been incorporated into clinical diagnostic criteria and commonly used in therapeutic trials. Current AD biomarkers fall into two categories: biomarkers of amyloid-β plaques and of tau-related neurodegeneration. Three of the five are imaging measures and two are cerebrospinal fluid analytes. AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping manner. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. In this Review, we discuss several time-dependent models of AD that take into consideration varying age of onset (early versus late) and the influence of aging and co-occurring brain pathologies that commonly arise in the elderly.
authors.affiliation: Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: jack.clifford@mayo.edu.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Neurology, Hope Center for Neurological Disorders, and Knight Alzheimer's Disease Research Center, Washington University, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: holtzman@neuro.wustl.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
mesh_terms: D000375:Aging / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D059906:Neuroimaging; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism; D058225:Plaque, Amyloid / Q000134:cerebrospinal fluid / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins