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Open Access 01-12-2015 | Research

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

Authors: Katarzyna Adamczuk, Jolien Schaeverbeke, Hugo M. J. Vanderstichele, Johan Lilja, Natalie Nelissen, Koen Van Laere, Patrick Dupont, Kelly Hilven, Koen Poesen, Rik Vandenberghe

Published in: Alzheimer's Research & Therapy | Issue 1/2015

Abstract

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 ¹⁸F-flutemetamol PET and CSF measurement of Aβ1-42, Aβ1-40, Aβ1-38, and total tau (ttau). ¹⁸F-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 ¹⁸F-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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Title: Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
Authors: Katarzyna Adamczuk
Jolien Schaeverbeke
Hugo M. J. Vanderstichele
Johan Lilja
Natalie Nelissen
Koen Van Laere
Patrick Dupont
Kelly Hilven
Koen Poesen
Rik Vandenberghe
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-015-0159-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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