title: A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging.
abstract: BACKGROUND
  Changes in cerebrospinal fluid (CSF) tau and amyloid β (Aβ)42 accompany development of Alzheimer's brain pathology. Robust tau and Aβ42 immunoassays were developed to establish a tau/Aβ42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects.
  
  
  METHODS
  A CSF tau/Aβ42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET. Performance was assessed using an independent validation cohort.
  
  
  RESULTS
  A tau/Aβ42 = 0.215 cutoff provided 94.8% sensitivity and 77.7% specificity. Concordance with PET visual reads was estimated at 86.9% in a ∼50% PET positive population. In the validation cohort, the cutoff demonstrated 78.4% sensitivity and 84.9% specificity to distinguish the AD and HC populations.
  
  
  CONCLUSIONS
  A tau/Aβ42 cutoff with acceptable sensitivity and specificity distinguished HC from mild-to-moderate AD subjects and maximized concordance to brain amyloidosis. The defined cutoff demonstrated that CSF analysis may be useful as a surrogate to imaging assessment of AD pathology.
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Mo
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Stromswold
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Wilson
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Holder
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Laterza
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Savage
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Arie
authors.initials: A
authors.lastname: Struyk
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Duke Neurology, Duke University, Durham, NC, USA.
authors.forename: James
authors.initials: J
authors.lastname: Burke
authors.affiliation: Commonwealth Scientific and Industrial Research Organization, Parkville, Victoria, Australia.
authors.forename: S Lance
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Bråthen
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Sigrid Botne
authors.initials: SB
authors.lastname: Sando
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Linda R
authors.initials: LR
authors.lastname: White
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Christy
authors.initials: C
authors.lastname: Weiss
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Cowes
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Bush
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Ganga
authors.initials: G
authors.lastname: DeSilva
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Darby
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Rainey-Smith
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Surls
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Sagini
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tanen
authors.affiliation: Luminex, Austin, TX, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Altman
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Johan
authors.initials: J
authors.lastname: Luthman
authors.affiliation: Merck & Co. Inc., Kenilworth, NJ, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Egan
keywords: Alzheimer's disease; Amyloid β42; Diagnostic test assessment; PET; Tau