title: Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy.
abstract: In vivo tau imaging may become a diagnostic marker for Alzheimer disease (AD) and provides insights into the pathophysiology of AD.
  
  
  
  To evaluate the usefulness of [18F]-AV-1451 positron emission tomography (PET) imaging to stage AD and assess the associations among β-amyloid (Aβ), tau, and volume loss.
  
  
  
  An imaging study conducted at Knight Alzheimer Disease Research Center at Washington University in St Louis, Missouri. A total of 59 participants who were cognitively normal (CN) (Clinical Dementia Rating [CDR] score, 0) or had AD dementia (CDR score, >0) were included.
  
  
  
  Standardized uptake value ratio (SUVR) of [18F]-AV-1451 in the hippocampus and a priori-defined AD cortical signature regions, cerebrospinal fluid Aβ42, hippocampal volume, and AD signature cortical thickness.
  
  
  
  Of the 59 participants, 38 (64%) were male; mean (SD) age was 74 (6) years. The [18F]-AV-1451 SUVR in the hippocampus and AD cortical signature regions distinguished AD from CN participants (area under the receiver operating characteristic curve range [95% CI], 0.89 [0.73-1.00] to 0.98 [0.92-1.00]). An [18F]-AV-1451 SUVR cutoff value of 1.19 (sensitivity, 100%; specificity, 86%) from AD cortical signature regions best separated cerebrospinal fluid Aβ42-positive (Aβ+) AD from cerebrospinal fluid Aβ42-negative (Aβ-) CN participants. This same cutoff also divided Aβ+ CN participants into low vs high tau groups. Moreover, the presence of Aβ+ was associated with an elevated [18F]-AV-1451 SUVR in AD cortical signature regions (Aβ+ participants: mean [SD], 1.3 [0.3]; Aβ- participants: 1.1 [0.1]; F = 4.3, P = .04) but not in the hippocampus. The presence of Aβ+ alone was not related to hippocampal volume or AD signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with volumetric loss in both the hippocampus and AD cortical signature regions. The observed [18F]-AV-1451 SUVR volumetric association was modified by Aβ status in the hippocampus but not in AD cortical signature regions. An inverse association between hippocampal [18F]-AV-1451 SUVR and volume was seen in Aβ+ participants (R2 = 0.55; P < .001) but not Aβ- (R2 = 0; P = .97) participants.
  
  
  
  Use of [18F]-AV-1451 has a potential for staging of the preclinical and clinical phases of AD. β-Amyloid interacts with hippocampal and cortical tauopathy to affect neurodegeneration. In the absence of Aβ, hippocampal tau deposition may be insufficient for the neurodegenerative process that leads to AD.
authors.affiliation: Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri3Department of Radiology, Washington University, St Louis, Missouri.
authors.forename: Tammie L
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: Department of Radiology, Washington University, St Louis, Missouri.
authors.forename: Yi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Radiology, Washington University, St Louis, Missouri.
authors.forename: Jon
authors.initials: J
authors.lastname: Christensen
authors.affiliation: Department of Radiology, Washington University, St Louis, Missouri.
authors.forename: Karl
authors.initials: K
authors.lastname: Friedrichsen
authors.affiliation: Department of Radiology, Washington University, St Louis, Missouri.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aldea
authors.affiliation: Department of Radiology, University of Alabama, Birmingham.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McConathy
authors.affiliation: Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri5The Hope Center for Neurological Disorders at Washington University, St Louis, Missouri.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri5The Hope Center for Neurological Disorders at Washington University, St Louis, Missouri.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Department of Neurology, Washington University, St Louis, Missouri2The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri3Department of Radiology, Washington University, St Louis, Missouri5The Hope Center for Neurological Disorders at Washington University, St Louis, Missouri.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017063:Outcome Assessment, Health Care; D010446:Peptide Fragments / Q000378:metabolism*; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index; D024801:Tauopathies / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D002243:Carbolines; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole