title: Origins of Alzheimer's disease:  reconciling cerebrospinal fluid biomarker and neuropathology data regarding the temporal sequence of amyloid-beta and tau involvement.
abstract: OBJECTIVE
  This review aims to address the temporal sequencing of involvement of amyloid-beta (Aβ) and tau in the pathogenesis of Alzheimer's disease and reconcile apparently conflicting neuropathologic and biomarker data.
  
  
  RESULTS
  Although neuropathologic studies show that limbic system tau disease occurs ubiquitously in middle-aged individuals before the appearance of amyloid plaques, biomarker studies in living individuals suggest that Aβ disease is the initiating event in Alzheimer's disease and precedes cerebrospinal fluid tau changes. Evidence from neuropathologic, biomarker, genetic and cellular/mouse studies shows that tau accumulation in limbic regions occurs slowly with age and does not induce widespread neurodegeneration, but that Aβ interacts with tau in some way to accelerate neurofibrillary disease and induce neurodegeneration.
  
  
  CONCLUSIONS
  Aβ aggregation is the key initial trigger of Alzheimer's disease pathologic changes and interacts with tau to exacerbate age-related tauopathy and induce neurodegeneration.
authors.affiliation: Department of Neurology, Hope Center for Neurologic Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Musiek
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins