eprintid: 10056835 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/05/68/35 datestamp: 2018-09-24 07:55:00 lastmod: 2021-10-04 00:01:52 status_changed: 2018-09-24 07:55:00 type: article metadata_visibility: show creators_name: Sogorb-Esteve, A creators_name: Garcia-Ayllon, M-S creators_name: Gobom, J creators_name: Alom, J creators_name: Zetterberg, H creators_name: Blennow, K creators_name: Saez-Valero, J title: Levels of ADAM10 are reduced in Alzheimer's disease CSF ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Science & Technology, Life Sciences & Biomedicine, Immunology, Neurosciences, Neurosciences & Neurology, AMYLOID PRECURSOR PROTEIN, MILD COGNITIVE IMPAIRMENT, ALPHA-SECRETASE ADAM10, HUMAN CEREBROSPINAL-FLUID, TACE ACTIVITY, BACE1 ACTIVITY, DISINTEGRIN, METALLOPROTEASE, IDENTIFICATION, DIMERIZATION note: © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. abstract: BACKGROUND: The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of the amyloid precursor protein. This study assesses whether ADAM10 is present in cerebrospinal fluid (CSF), and whether it has potential as a biomarker for Alzheimer’s disease (AD). METHODS: ADAM10 was characterized in human CSF samples by immunoprecipitation and western blotting using antibodies specific for different domains of the protein and by ultracentrifugation in sucrose density gradients. Samples from AD patients (n = 20) and age-matched non-AD controls (n = 20) were characterized for classical CSF biomarkers, Aβ42, T-tau, or P-tau by ELISA, and assayed for soluble ADAM10 levels by western blotting. RESULTS: We found that ADAM10 is present in human CSF as several distinct species: an immature form retaining the prodomain (proADAM10; ~ 80 kDa), a mature unprocessed full-length form (ADAM10f; ~ 55 kDa), and a truncated large soluble form released from the membrane (sADAM10; ~ 50 kDa). Fractionation by ultracentrifugation on sucrose density gradients showed that the ADAM10f and sADAM10 species form large complexes. Immunoblotting revealed a significant decrease in ADAM10f and sADAM10 in AD CSF compared to control CSF, while proADAM10 levels remained unaltered. CONCLUSIONS: Several forms of ADAM10 are present in CSF, mainly assembled as high-molecular weight complexes. The determination of the levels of mature forms of CSF-ADAM10 may be useful as a biomarker for AD. date: 2018-07-25 date_type: published publisher: BMC official_url: https://doi.org/10.1186/s12974-018-1255-9 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1571566 doi: 10.1186/s12974-018-1255-9 lyricists_name: Sogorb Esteve, Aitana lyricists_name: Zetterberg, Henrik lyricists_id: AASOG25 lyricists_id: HZETT94 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: Journal of Neuroinflammation volume: 15 article_number: 213 pages: 9 issn: 1742-2094 citation: Sogorb-Esteve, A; Garcia-Ayllon, M-S; Gobom, J; Alom, J; Zetterberg, H; Blennow, K; Saez-Valero, J; (2018) Levels of ADAM10 are reduced in Alzheimer's disease CSF. Journal of Neuroinflammation , 15 , Article 213. 10.1186/s12974-018-1255-9 <https://doi.org/10.1186/s12974-018-1255-9>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10056835/1/s12974-018-1255-9.pdf