Title: Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease
Authors: Adamczuk, Katarzyna
Schaeverbeke, Jolien
Vanderstichele, Hugo
Lilja, Johan
Nelissen, Natalie
Van Laere, Koen
Dupont, Patrick
Hilven, Kelly
Poesen, Koen
Vandenberghe, Rik # ×
Issue Date: 18-Dec-2015
Publisher: BioMed Central Ltd.
Series Title: Alzheimer's Research & Therapy vol:18 issue:7 pages:75-86
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 (SUVRcomp) with reference to cerebellar grey
matter. Based on a prior autopsy validation study, the SUVRcomp 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.
ISSN: 1758-9193
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Cognitive Neurology
Nuclear Medicine & Molecular Imaging
Laboratory for Neuroimmunology
Laboratory for Molecular Neurobiomarker Research
× corresponding author
# (joint) last author

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