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Acta Neuropathologica
Published in: Acta Neuropathologica 1/2012

01-07-2012 | Original Paper

CSF biomarkers cutoffs: the importance of coincident neuropathological diseases

Authors: Jon B. Toledo, Johannes Brettschneider, Murray Grossman, Steven E. Arnold, William T. Hu, Sharon X. Xie, Virginia M.-Y. Lee, Leslie M. Shaw, John Q. Trojanowski

Published in: Acta Neuropathologica | Issue 1/2012

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Abstract

The effects of applying clinical versus neuropathological diagnosis and the inclusion of cases with coincident neuropathological diagnoses have not been assessed specifically when studying cerebrospinal fluid (CSF) biomarker classification cutoffs for patients with neurodegenerative diseases that cause dementia. Thus, 142 neuropathologically diagnosed neurodegenerative dementia patients [71 Alzheimer’s disease (AD), 29 frontotemporal lobar degeneration (FTLD), 3 amyotrophic lateral sclerosis, 7 dementia with Lewy bodies, 32 of which cases also had coincident diagnoses] were studied. 96 % had enzyme-linked immunosorbant assay (ELISA) CSF data and 77 % had Luminex CSF data, with 43 and 46 controls for comparison, respectively. Aβ42, total, and phosphorylated tau181 were measured. Clinical and neuropathological diagnoses showed an 81.4 % overall agreement. Both assays showed high sensitivity and specificity to classify AD subjects against FTLD subjects and controls, and moderate sensitivity and specificity for classifying FTLD subjects against controls. However, among the cases with neuropathological diagnoses of AD plus another pathology (26.8 % of the sample), 69.4 % (ELISA) and 96.4 % (Luminex) were classified as AD according to their biomarker profiles. Use of clinical diagnosis instead of neuropathological diagnosis led to a 14–17 % underestimation of the biomarker accuracy. These results show that while CSF Aβ and tau assays are useful for diagnosis of AD and neurodegenerative diseases even at MCI stages, CSF diagnostic analyte panels that establish a positive diagnosis of Lewy body disease and FTLD are also needed, and must be established based on neuropathological rather than clinical diagnoses.
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Metadata
Title
CSF biomarkers cutoffs: the importance of coincident neuropathological diseases
Authors
Jon B. Toledo
Johannes Brettschneider
Murray Grossman
Steven E. Arnold
William T. Hu
Sharon X. Xie
Virginia M.-Y. Lee
Leslie M. Shaw
John Q. Trojanowski
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 1/2012
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-012-0983-7

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