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Improved Differential Diagnosis of Alzheimer’s Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers

Khoonsari, PE; Shevchenko, G; Herman, S; Remnestål, J; Giedraitis, V; Brundin, R; Gunnarsson, MD; ... Kultima, K; + view all (2019) Improved Differential Diagnosis of Alzheimer’s Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers. Journal of Alzheimer's Disease , 67 (2) pp. 639-651. 10.3233/JAD-180855. Green open access

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Abstract

BACKGROUND: Alzheimer’s disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: Aβ₄₂, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. OBJECTIVE: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. METHODS: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4–9 years and 21 of these converted to AD, whereas 53 remained stable. RESULTS: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCI/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. CONCLUSIONS: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.

Type: Article
Title: Improved Differential Diagnosis of Alzheimer’s Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JAD-180855
Publisher version: http://dx.doi.org/10.3233/JAD-180855
Language: English
Additional information: © 2019 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/legalcode).
Keywords: Alzheimer’s disease, ELISA, cerebrospinal fluid, mass spectrometry, mild cognitive impairment, proteomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10067050
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