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Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease

INTRODUCTION: In this study of preclinical Alzheimer’s disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) Aβ ratios rather than Aβ42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). METHODS: Thirty-eight commun...

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Autores principales: Adamczuk, Katarzyna, Schaeverbeke, Jolien, Vanderstichele, Hugo M. J., Lilja, Johan, Nelissen, Natalie, Van Laere, Koen, Dupont, Patrick, Hilven, Kelly, Poesen, Koen, Vandenberghe, Rik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683859/
https://www.ncbi.nlm.nih.gov/pubmed/26677842
http://dx.doi.org/10.1186/s13195-015-0159-5
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author Adamczuk, Katarzyna
Schaeverbeke, Jolien
Vanderstichele, Hugo M. J.
Lilja, Johan
Nelissen, Natalie
Van Laere, Koen
Dupont, Patrick
Hilven, Kelly
Poesen, Koen
Vandenberghe, Rik
author_facet Adamczuk, Katarzyna
Schaeverbeke, Jolien
Vanderstichele, Hugo M. J.
Lilja, Johan
Nelissen, Natalie
Van Laere, Koen
Dupont, Patrick
Hilven, Kelly
Poesen, Koen
Vandenberghe, Rik
author_sort Adamczuk, Katarzyna
collection PubMed
description INTRODUCTION: In this study of preclinical Alzheimer’s disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) Aβ ratios rather than Aβ42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). METHODS: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65–80 years) underwent (18)F-flutemetamol PET and CSF measurement of Aβ1-42, Aβ1-40, Aβ1-38, and total tau (ttau). (18)F-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVR(comp)) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVR(comp) cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and (18)F-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. RESULTS: Seven out of 38 subjects (18 %) were positive on amyloid PET. Aβ42/ttau, Aβ42/Aβ40, Aβ42/Aβ38, and Aβ42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) ≥ 0.908). Aβ40 and Aβ38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, Aβ42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of Aβ42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). CONCLUSION: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of Aβ42/ttau rather than using Aβ42 in isolation.
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spelling pubmed-46838592015-12-19 Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease Adamczuk, Katarzyna Schaeverbeke, Jolien Vanderstichele, Hugo M. J. Lilja, Johan Nelissen, Natalie Van Laere, Koen Dupont, Patrick Hilven, Kelly Poesen, Koen Vandenberghe, Rik Alzheimers Res Ther Research INTRODUCTION: In this study of preclinical Alzheimer’s disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) Aβ ratios rather than Aβ42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). METHODS: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65–80 years) underwent (18)F-flutemetamol PET and CSF measurement of Aβ1-42, Aβ1-40, Aβ1-38, and total tau (ttau). (18)F-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVR(comp)) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVR(comp) cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and (18)F-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. RESULTS: Seven out of 38 subjects (18 %) were positive on amyloid PET. Aβ42/ttau, Aβ42/Aβ40, Aβ42/Aβ38, and Aβ42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) ≥ 0.908). Aβ40 and Aβ38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, Aβ42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of Aβ42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). CONCLUSION: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of Aβ42/ttau rather than using Aβ42 in isolation. BioMed Central 2015-12-18 /pmc/articles/PMC4683859/ /pubmed/26677842 http://dx.doi.org/10.1186/s13195-015-0159-5 Text en © Adamczuk et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Adamczuk, Katarzyna
Schaeverbeke, Jolien
Vanderstichele, Hugo M. J.
Lilja, Johan
Nelissen, Natalie
Van Laere, Koen
Dupont, Patrick
Hilven, Kelly
Poesen, Koen
Vandenberghe, Rik
Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
title Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
title_full Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
title_fullStr Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
title_full_unstemmed Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
title_short Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
title_sort diagnostic value of cerebrospinal fluid aβ ratios in preclinical alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683859/
https://www.ncbi.nlm.nih.gov/pubmed/26677842
http://dx.doi.org/10.1186/s13195-015-0159-5
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