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A novel ELISA for the measurement of cerebrospinal fluid SNAP-25 in patients with Alzheimer's disease

Öhrfelt, A; Brinkmalm, A; Dumurgier, J; Zetterberg, H; Bouaziz-Amar, E; Hugon, J; Paquet, C; (2018) A novel ELISA for the measurement of cerebrospinal fluid SNAP-25 in patients with Alzheimer's disease. Neuroscience 10.1016/j.neuroscience.2018.11.038. (In press). Green open access

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Abstract

Synaptic degeneration is central in Alzheimer's disease (AD) pathogenesis and biomarkers to monitor this pathophysiology in living patients are warranted. We developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for the measurement of the pre-synaptic protein SNAP-25 in cerebrospinal fluid (CSF) and evaluated it as a biomarker for AD. CSF samples included a pilot study consisting of AD (N=26) and controls (N=26), and two independent clinical cohorts of AD patients and controls. Cohort I included CSF samples from patients with dementia due to AD (N=17), patients with mild cognitive impairment (MCI) due to AD (N=5) and controls (N=17), and cohort II CSF samples from patients with dementia due to AD (N=24), patients with MCI due to AD (N=18) and controls (N=36). CSF levels of SNAP-25 were significantly increased in patients with AD compared with controls (P≤0.00001). In both clinical cohorts, CSF levels of SNAP-25 were significantly increased in patients with MCI due to AD (P<0.0001). SNAP-25 could differentiate dementia due to AD (N=41) from controls (N=52) and MCI due to AD (N=23) from controls (N=52) with areas under the curve of 0.967 (P<0.0001) and 0.948 (P<0.0001), respectively. CSF SNAP-25 is a promising AD biomarker that differentiates AD patients in different clinical stages of the disease from controls with excellent diagnostic accuracy. Future studies should address the specificity of the CSF SNAP-25 against common differential diagnoses to AD, as well as how the biomarker changes in response to treatment with disease-modifying drug candidates.

Type: Article
Title: A novel ELISA for the measurement of cerebrospinal fluid SNAP-25 in patients with Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroscience.2018.11.038
Publisher version: https://doi.org/10.1016/j.neuroscience.2018.11.038
Language: English
Additional information: © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Alzheimer’s disease, Biomarker, Cerebrospinal fluid, ELISA, Mild cognitive impairment, SNAP-25
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/10064190
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