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Cited by 116Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

Comparison of Cerebrospinal Fluid Levels of Tau and Aβ 1-42 in Alzheimer Disease and Frontotemporal Degeneration Using 2 Analytical Platforms

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Irwin, David J., McMillan, Corey T., Toledo, Jon B., Arnold, Steven E., Shaw, Leslie M., Wang, Li-San, Van Deerlin, Vivianna, Lee, Virginia M.-Y. +2 more·2012·Archives of Neurology
DOI 10.1001/archneurol.2012.26PMC PMC3528180
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Abstract

OBJECTIVE: To use values of cerebrospinal fluid tau and β-amyloid obtained from 2 different analytical immunoassays to differentiate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD). DESIGN: Cerebrospinal fluid values of total tau (T-tau) and β-amyloid 1-42 (Aβ 1-42) obtained using the Innotest enzyme-linked immunosorbent assay were transformed using a linear regression model to equivalent values obtained using the INNO-BIA AlzBio3 (xMAP; Luminex) assay. Cutoff values obtained from the xMAP assay were developed in a series of autopsy-confirmed cases and cross validated in another series of autopsy-confirmed samples using transformed enzyme-linked immunosorbent assay values to assess sensitivity and specificity for differentiating AD from FTLD. SETTING: Tertiary memory disorder clinics and neuropathologic and biomarker core centers. PARTICIPANTS: Seventy-five samples from patients with cerebrospinal fluid data obtained from both assays were used for transformation of enzyme-linked immunosorbent assay values. Forty autopsy-confirmed cases (30 with AD and 10 with FTLD) were used to establish diagnostic cutoff values and then cross validated in a second sample set of 21 autopsy-confirmed cases (11 with AD and 10 with FTLD) with transformed enzyme-linked immunosorbent assay values. MAIN OUTCOME MEASURE: Diagnostic accuracy using transformed biomarker values. RESULTS: Data obtained from both assays were highly correlated. The T-tau to Aβ 1-42 ratio had the highest correlation between measures (r = 0.928, P < .001) and high reliability of transformation (intraclass correlation coefficient= 0.89). A cutoff of 0.34 for the T-tau to Aβ 1-42 ratio had 90% and 100% sensitivity and 96.7% and 91% specificity to differentiate FTLD cases in the validation and cross-validation samples, respectively. CONCLUSIONS: Values from 2 analytical platforms can be transformed into equivalent units, which can distinguish AD from FTLD more accurately than the clinical diagnosis.

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  • Patients were included if they had either a post mortem neuropathologic diagnosis or an in vivo CSF analyte profile suggestive of the underlying neuropathology based on cutoffs previously validated in autopsy series.

    “Patients were included if they had either a post mortem neuropathologic diagnosis or an in vivo CSF analyte profile suggestive of the underlying neuropathology based on cutoffs previously validated in autopsy series.”

    From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [28]

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References 51 · Cited by 116

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  1. [1]Johnson JK Head E Kim R Starr A Cotman CW Clinical and pathological evidence for a frontal variant of Alzheimer disease Arch Neurol 10 1999 56 10 1233 1239 10520939
  2. [2]Grossman M Libon DJ Forman MS Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia Arch Neurol 11 2007 64 11 1601 1609 17998442
  3. [4]Hu WT McMillan C Libon D Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia Neurology 17 8 2010 75 7 595 602 20713948 PMC2931765
  4. [5]Grossman M Primary progressive aphasia: clinicopathological correlations Nat Rev Neurol 2 2010 6 2 88 97 20139998 PMC3637977
  5. [6]Forman MS Farmer J Johnson JK Frontotemporal dementia: clinicopathological correlations Ann Neurol 6 2006 59 6 952 962 16718704 PMC2629792
  6. [7]Graham A Davies R Xuereb J Pathologically proven frontotemporal dementia presenting with severe amnesia Brain 3 2005 128 Pt 3 597 605 15634737
  7. [9]McKhann GM Knopman DS Chertkow H The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease Alzheimers Dement 5 2011 7 3 263 269 21514250 PMC3312024
  8. [10]Rascovsky K Hodges JR Knopman D Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia Brain 2 8 2011 PMC3170532 21810890
  9. [11]Gorno-Tempini ML Hillis AE Weintraub S Classification of primary progressive aphasia and its variants Neurology 15 3 2011 76 11 1006 1014 21325651 PMC3059138
  10. [12]Weiner MW Aisen PS Jack CR Jr. The Alzheimer’s disease neuroimaging initiative: progress report and future plans Alzheimers Dement 5 2010 6 3 202 211 e207 20451868 PMC2927112
  11. [15]Shaw LM Vanderstichele H Knapik-Czajka M Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI Acta Neuropathol 5 2011 121 5 597 609 21311900 PMC3175107
  12. [16]Trojanowski JQ Vandeerstichele H Korecka M Update on the biomarker core of the Alzheimer’s Disease Neuroimaging Initiative subjects Alzheimers Dement 5 2010 6 3 230 238 20451871 PMC2867838
  13. [17]van Harten AC Kester MI Visser PJ Tau and p-tau as CSF biomarkers in dementia: a meta-analysis Clin Chem Lab Med 3 2011 49 3 353 366 21342021
  14. [18]Pijnenburg YA Schoonenboom NS Rosso SM CSF tau and Abeta42 are not useful in the diagnosis of frontotemporal lobar degeneration Neurology 11 5 2004 62 9 1649 15136709
  15. [19]Arai H Morikawa Y Higuchi M Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology Biochem Biophys Res Commun 18 7 1997 236 2 262 264 9240421
  16. [20]Green AJ Harvey RJ Thompson EJ Rossor MN Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer’s disease Neurosci Lett 8 1 1999 259 2 133 135 10025576
  17. [21]Riemenschneider M Wagenpfeil S Diehl J Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration Neurology 11 6 2002 58 11 1622 1628 12058089
  18. [22]Kapaki E Paraskevas GP Papageorgiou SG Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration Alzheimer Dis Assoc Disord Jan-Mar 2008 22 1 47 53 18317246
  19. [23]de Souza LC Lamari F Belliard S Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer’s disease from other cortical dementias J Neurol Neurosurg Psychiatry 3 2011 82 3 240 246 20802215
  20. [24]Sjogren M Minthon L Davidsson P CSF levels of tau, beta-amyloid(1-42) and GAP-43 in frontotemporal dementia, other types of dementia and normal aging J Neural Transm 2000 107 5 563 579 11072752
  21. [27]Bian H Grossman M Frontotemporal lobar degeneration: recent progress in antemortem diagnosis Acta Neuropathol 7 2007 114 1 23 29 17541785
  22. [28]Olsson A Vanderstichele H Andreasen N Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology Clin Chem 2 2005 51 2 336 345 15563479
  23. [29]Fagan AM Shaw LM Xiong C Comparison of Analytical Platforms for Cerebrospinal Fluid Measures of {beta}-Amyloid 1-42, Total tau, and P-tau181 for Identifying Alzheimer Disease Amyloid Plaque Pathology Arch Neurol 9 5 2011 PMC3154969 21555603
  24. [30]Xie SX Baek Y Grossman M Building an integrated neurodegenerative disease database at an academic health center Alzheimers Dement 7 2011 7 4 e84 e93 21784346 PMC3145967
  25. [31]Hu WT Chen-Plotkin A Arnold SE Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment Acta Neuropathol 6 2010 119 6 669 678 20232070 PMC2880811
  26. [32]Mackenzie IR Neumann M Bigio EH Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update Acta Neuropathol 1 2010 119 1 1 4 19924424 PMC2799633
  27. [33]Hyman BT Trojanowski JQ Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease J Neuropathol Exp Neurol 10 1997 56 10 1095 1097 9329452
  28. [34]McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease Neurology 7 1984 34 7 939 944 6610841
  29. [36]Winton MJ Lee EB Sun E Intraneuronal APP, not free Abeta peptides in 3xTg-AD mice: implications for tau versus Abeta-mediated Alzheimer neurodegeneration J Neurosci 25 5 2011 31 21 7691 7699 21613482 PMC3118598
  30. [38]Lewczuk P Zimmermann R Wiltfang J Kornhuber J Neurochemical dementia diagnostics: a simple algorithm for interpretation of the CSF biomarkers J Neural Transm 9 2009 116 9 1163 1167 19653063
  31. [39]Reijn TS Rikkert MO van Geel WJ de Jong D Verbeek MM Diagnostic accuracy of ELISA and xMAP technology for analysis of amyloid beta(42) and tau proteins Clin Chem 5 2007 53 5 859 865 17395712
  32. [40]Wang L LY Chang S Leight S Malgorzata KC Shaw L Lee VMY Trojanowski JQ Clark C Comparison of xMAP and ELISA assays for detecting CSF biomarkers of Alzheimer’s Disease Journal of Alzheimer’s disease 2011 under review PMC3660971 22571982
  33. [41]Mirra SS Heyman A McKeel D The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease Neurology 4 1991 41 4 479 486 2011243
  34. [43]Kipps CM Hodges JR Hornberger M Nonprogressive behavioural frontotemporal dementia: recent developments and clinical implications of the ‘bvFTD phenocopy syndrome’ Curr Opin Neurol 12 2010 23 6 628 632 20962637
  35. [44]Toledo JB BJ Grossman M Arnold SE Hu WT Xie S Lee VMY Shaw LM Trojanowski JQ Improving diagnostic accuracy for dementia: CSF biomarker cutoffs based on clinical and neuropathological criteria Annals of Neurology 2011 under review
  36. [45]Seguin J Formaglio M Perret-Liaudet A CSF biomarkers in posterior cortical atrophy Neurology 24 5 2011 76 21 1782 1788 21525425
  37. [46]Koric L Felician O Ceccaldi M [Use of CSF biomarkers in the diagnosis of Alzheimer’s disease in clinical practice] Rev Neurol (Paris) Jun-Jul 2010 167 6-7 474 484 21420704
  38. [47]Roberson ED Hesse JH Rose KD Frontotemporal dementia progresses to death faster than Alzheimer disease Neurology 13 9 2005 65 5 719 725 16157905
  39. [48]Jack CR Jr. Knopman DS Jagust WJ Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade Lancet Neurol 1 2010 9 1 119 128 20083042 PMC2819840
  40. [49]Vemuri P Wiste HJ Weigand SD Serial MRI and CSF biomarkers in normal aging, MCI, and AD Neurology 13 7 2010 75 2 143 151 20625167 PMC2905929
  41. [50]Mattsson N Andreasson U Persson S The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers Alzheimers Dement 7 2011 7 4 386 395 e386 21784349 PMC3710290
  42. [51]Hu WT Chen-Plotkin A Grossman M Novel CSF biomarkers for frontotemporal lobar degenerations Neurology 7 12 2010 75 23 2079 2086 21048198 PMC2995537
  43. [52]Hu WT Chen-Plotkin A Arnold SE Biomarker discovery for Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease Acta Neuropathol 9 2010 120 3 385 399 20652578 PMC2982700

Authors
Irwin, D. J., McMillan, C. T., Toledo, J. B., Arnold, S. E., Shaw, L. M., Wang, L.-S., Van Deerlin, V., Lee, V. M.-Y., Trojanowski, J. Q., & Grossman, M.
Affiliations
University of Pennsylvania (US)
Corresponding author
Grossman, Murray
ORCID
Venue
Archives of Neurology
Publisher
American Medical Association (AMA)
Published
2012-08-01
Volume
69
Issue
8
Pages
1018-25
ISSN
0003-9942 (ISSN-L)
DOI
10.1001/archneurol.2012.26
PMC
PMC3528180
OpenAlex
W2141349376
Cited by
116
References
51
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 10 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 12 · 2016: 9 · 2015: 11 · 2014: 13 · 2013: 8 · 2012: 8
FWCI
9.14
Type
journal article
Language
en
Open access
Locations
  • Archives of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01-AG15116, P30AG010124, R01AG015116, P01AG017586, P01-AG32953, P01AG032953, P01AG019724, T32AG000255)
  • National Institute of Neurological Disorders and Stroke (R01-NS44266, P50NS053488, R01NS044266, P01 NS53488)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
Alzheimer's disease, frontotemporal lobar degeneration, cerebrospinal fluid biomarkers, tau protein, amyloid-beta 42, immunoassay comparison, diagnostic thresholds, differential diagnosis, diagnostic accuracy
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Frontotemporal Lobar Degeneration

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