title: Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes.
abstract: BACKGROUND
  We aimed to assess the feasibility of determining Alzheimer's disease cerebrospinal fluid (CSF) cut points in small samples through comparison with amyloid positron emission tomography (PET).
  
  
  METHODS
  Twenty-three individuals (19 patients, four controls) had CSF measures of amyloid beta (Aβ)1-42and total tau/Aβ1-42ratio, and florbetapir PET. We compared CSF measures with visual and quantitative (standardized uptake value ratio [SUVR]) PET measures of amyloid.
  
  
  RESULTS
  Seventeen of 23 were amyloid-positive on visual reads, and 14 of 23 at an SUVR of ≥1.1. There was concordance (positive/negative on both measures) in 20 of 23, of whom 19 of 20 were correctly classified at an Aβ1-42of 630 ng/L, and 20 of 20 on tau/Aβ1-42ratio (positive ≥0.88; negative ≤0.34). Three discordant cases had Aβ1-42levels between 403 and 729 ng/L and tau/Aβ1-42ratios of 0.54-0.58.
  
  
  CONCLUSIONS
  Comparing amyloid PET and CSF biomarkers provides a means of assessing CSF cut points in vivo, and can be applied to small sample sizes. CSF tau/Aβ1-42ratio appears robust at predicting amyloid status, although there are gray zones where there remains diagnostic uncertainty.
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Philip S J
authors.initials: PS
authors.lastname: Weston
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Ross W
authors.initials: RW
authors.lastname: Paterson
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; Transitional Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Modat
authors.affiliation: Transitional Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Ninon
authors.initials: N
authors.lastname: Burgos
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; Transitional Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Cardoso
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Magdalinou
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Manja
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Institute of Nuclear Medicine, University College London Hospitals, London, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Dickson
authors.affiliation: Institute of Nuclear Medicine, University College London Hospitals, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Barnes
authors.affiliation: Institute of Nuclear Medicine, University College London Hospitals, London, UK.
authors.forename: Jamshed B
authors.initials: JB
authors.lastname: Bomanji
authors.affiliation: Institute of Nuclear Medicine, University College London Hospitals, London, UK.
authors.forename: Irfan
authors.initials: I
authors.lastname: Kayani
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Cash
authors.affiliation: Transitional Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.affiliation: MRC Centre for Neuromuscular Disease, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Toombs
authors.affiliation: MRC Centre for Neuromuscular Disease, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lunn
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Mummery
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Martin N
authors.initials: MN
authors.lastname: Rossor
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.affiliation: MRC Centre for Neuromuscular Disease, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK; Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
keywords: Amyloid PET; Aβ; Cerebrospinal fluid; Cut points; Diagnosis; Phosphorylated tau; Tau
references.citation: Arch Neurol. 2007 Mar;64(3):343-9
references.pmid: 17210801
references.citation: J Nucl Med. 2012 Mar;53(3):378-84
references.pmid: 22331215
references.citation: Alzheimers Dement. 2013 May;9(3):251-61
references.pmid: 23622690
references.citation: JAMA Neurol. 2015 May;72 (5):571-81
references.pmid: 25822737
references.citation: Ann Neurol. 2010 Dec;68(6):825-34
references.pmid: 21181717
references.citation: Med Image Comput Comput Assist Interv. 2012;15(Pt 2):262-70
references.pmid: 23286057
references.citation: Curr Alzheimer Res. 2011 May;8(3):266-72
references.pmid: 21222598
references.citation: Lancet Neurol. 2014 Jun;13(6):614-29
references.pmid: 24849862
references.citation: Brain. 2015 May;138(Pt 5):1327-38
references.pmid: 25693589
references.citation: Lancet Neurol. 2003 Oct;2(10):605-13
references.pmid: 14505582
references.citation: Alzheimers Dement. 2015 Aug;11(8):964-74
references.pmid: 25824567
references.citation: Eur J Nucl Med Mol Imaging. 2015 Aug;42(9):1447-58
references.pmid: 26105119
references.citation: J Neurol. 2015 Dec;262(12):2722-30
references.pmid: 26410752
references.citation: Alzheimers Dement. 2011 May;7(3):263-9
references.pmid: 21514250
references.citation: JAMA Neurol. 2014 Oct;71(10 ):1282-9
references.pmid: 25155658
references.citation: Brain. 2015 Jul;138(Pt 7):2020-33
references.pmid: 25953778
references.citation: Dement Geriatr Cogn Disord. 2013;36(3-4):242-50
references.pmid: 23949210
references.citation: Ann Neurol. 2013 Dec;74(6):826-36
references.pmid: 23536396
references.citation: J Alzheimers Dis. 2014;41(3):801-7
references.pmid: 24705549
references.citation: Biomark Med. 2012 Aug;6(4):391-400
references.pmid: 22917141
references.citation: Alzheimers Dement. 2014 Nov;10(6):713-723.e2
references.pmid: 24721526
references.citation: Lancet Neurol. 2012 Feb;11(2):170-8
references.pmid: 22265212
references.citation: Brain. 2015 Mar;138(Pt 3):772-83
references.pmid: 25541191
references.citation: Neurology. 1995 Mar;45(3 Pt 1):461-6
references.pmid: 7898697
references.citation: Alzheimers Dement. 2015 Aug;11(8):986-93
references.pmid: 25916563
references.citation: JAMA. 2011 Jan 19;305(3):275-83
references.pmid: 21245183
references.citation: Alzheimers Dement. 2012 Jan;8(1):65-73
references.pmid: 22047631
references.citation: J Alzheimers Dis. 2013;36(4):759-67
references.pmid: 23666174