title: Comparison of two methods for the analysis of CSF Aβ and tau in the diagnosis of Alzheimer's disease.
abstract: BACKGROUND
  Biomarkers represent a promising adjunct to clinical techniques in the diagnosis of Alzheimer's Disease (AD) and other neurodegenerative diseases. At present, the potential of cerebrospinal fluid (CSF) biomarkers in diagnosing AD has been suggested but the degree of clinical utility is yet to be defined due to variability between studies. In this paper we compare the performance of two cerebrospinal fluid assay methods in predicting clinically diagnosed AD.
  
  
  METHODS
  CSF biomarker concentrations for Aβ1-42, P-tau181P and T-tau were analysed using INNOTEST (ELISA) and INNO-BIA AlzBio3 (Luminex) assay methods from Innogenetics, Belgium. Patients were clinically diagnosed based on NINCDS-ADRDA criteria supplemented with structural MRI, (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) and cognitive profiling.
  
  
  RESULTS
  An abnormally low Aβ1-42 was the most useful biomarker in predicting clinical AD. Depending on the assay method, the predictive accuracy remained constant or improved slightly when abnormalities in P-tau181P and T-tau were considered in addition to Aβ1-42. The Luminex method with our optimised reference concentrations performed best for patients ≤ 65 years with sensitivity = 1 and a specificity = 0.60 for both Aβ1-42 and when one or more abnormal biomarkers were considered.
  
  
  CONCLUSIONS
  Given accurate, robust and reproducible CSF analytical methods, of which the Luminex method seems the most useful and practicable, our investigation suggests that measuring CSF Aβ1-42, P-tau and T-tau has utility in the diagnosis of probable AD and, when used with clinical diagnostic techniques, seems especially helpful in the diagnosis of AD with onset prior to the age of 65 years.
authors: Neurodegenerative Disorders Research Pty Ltd 4 Lawrence Ave, West Perth, Western Australia.
authors: Matthew
authors: M
authors: Faull
authors: Department of Clinical Biochemistry, Pathwest Laboratory Medicine WA, QEII Medical Centre Nedlands, Western Australia.
authors: Simon Yl
authors: SY
authors: Ching
authors: Neurodegenerative Disorders Research Pty Ltd 4 Lawrence Ave, West Perth, Western Australia.
authors: Anna I
authors: AI
authors: Jarmolowicz
authors: Department of Clinical Biochemistry, Pathwest Laboratory Medicine WA, QEII Medical Centre Nedlands, Western Australia.
authors: John
authors: J
authors: Beilby
authors: Neurodegenerative Disorders Research Pty Ltd 4 Lawrence Ave, West Perth, Western Australia ; School of Medicine and Pharmacology, The University of Western Australia Nedlands, Western Australia.
authors: Peter K
authors: PK
authors: Panegyres
keywords: Alzheimer’s disease; P-tau; T-tau; amyloid beta; biomarkers; cerebrospinal fluid; clinical diagnosis; tau
references: Arch Neurol. 2012 Nov;69(11):1445-52
references: 22925882
references: Eur Neurol. 2009;62(4):200-3
references: 19602894
references: Expert Rev Proteomics. 2011 Aug;8(4):447-58
references: 21819301
references: Acta Neuropathol. 2007 Feb;113(2):107-17
references: 17089134
references: JAMA Neurol. 2013 Oct;70(10):1277-87
references: 23979011
references: Alzheimers Dement. 2014 May;10(3):381-92
references: 23850330
references: Arch Neurol. 2012 Nov;69(11):1407-8
references: 22926002
references: Front Aging Neurosci. 2014 Mar 24;6:47
references: 24715863
references: J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9
references: 22002422
references: Nat Rev Neurol. 2010 Mar;6(3):131-44
references: 20157306
references: PLoS One. 2011;6(7):e21896
references: 21814561
references: J Neuropathol Exp Neurol. 2012 Apr;71(4):266-73
references: 22437338
references: Lancet Neurol. 2006 Mar;5(3):228-34
references: 16488378
references: Neurobiol Aging. 2013 Dec;34(12 ):2815-26
references: 23890839
references: Neurology. 2012 Feb 14;78(7):468-76
references: 22302554
references: J Nutr Health Aging. 2013 Jan;17(1):54-63
references: 23299381
references: Lancet Neurol. 2007 Aug;6(8):734-46
references: 17616482
references: Neurology. 2007 Dec 11;69(24):2197-204
references: 17568013
references: Alzheimers Dement. 2012 Nov;8(6):520-7
references: 22677492
references: Neurobiol Aging. 2012 Jul;33(7):1203-14
references: 21159408
references: Neurology. 2004 Apr 13;62(7):1141-7
references: 15079014
references: Am J Alzheimers Dis Other Demen. 2007 Feb-Mar;22(1):48-56
references: 17534002
references: Clin Chem. 2013 Jun;59(6):903-16
references: 23519967
references: Am J Alzheimers Dis Other Demen. 2013 Jun;28(4):337-47
references: 23687179
references: Biomark Med. 2009 Dec;3(6):735-7
references: 20477711
references: Alzheimers Res Ther. 2010 May 07;2(2):11
references: 20497615
references: Methods. 2012 Apr;56(4):484-93
references: 22503777
references: Alzheimers Dement. 2012 Jan;8(1):65-73
references: 22047631
references: Neurobiol Aging. 2008 Aug;29(8):1143-59
references: 17428581
references: Alzheimers Dement. 2012 Jul;8(4):312-36
references: 22748938
references: Neurology. 2005 Dec 27;65(12):1863-72
references: 16237129