eprintid: 10064190 rev_number: 17 eprint_status: archive userid: 608 dir: disk0/10/06/41/90 datestamp: 2018-12-17 08:30:34 lastmod: 2021-10-15 22:29:52 status_changed: 2018-12-17 08:30:34 type: article metadata_visibility: show creators_name: Öhrfelt, A creators_name: Brinkmalm, A creators_name: Dumurgier, J creators_name: Zetterberg, H creators_name: Bouaziz-Amar, E creators_name: Hugon, J creators_name: Paquet, C creators_name: Blennow, K title: A novel ELISA for the measurement of cerebrospinal fluid SNAP-25 in patients with Alzheimer's disease ispublished: inpress divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Alzheimer’s disease, Biomarker, Cerebrospinal fluid, ELISA, Mild cognitive impairment, SNAP-25 note: © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 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. date: 2018 date_type: published official_url: https://doi.org/10.1016/j.neuroscience.2018.11.038 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1608823 doi: 10.1016/j.neuroscience.2018.11.038 pii: S0306-4522(18)30780-2 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Neuroscience event_location: United States issn: 1873-7544 citation: Öhrfelt, A; Brinkmalm, A; Dumurgier, J; Zetterberg, H; Bouaziz-Amar, E; Hugon, J; Paquet, C; Öhrfelt, A; Brinkmalm, A; Dumurgier, J; Zetterberg, H; Bouaziz-Amar, E; Hugon, J; Paquet, C; Blennow, K; - view fewer <#> (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 <https://doi.org/10.1016/j.neuroscience.2018.11.038>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10064190/1/1-s2.0-S0306452218307802-main.pdf