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.
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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-pp.ucl.ac.uk/id/eprint/10067050 |
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