TY  - JOUR
JF  - Journal of Neuroinflammation
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Immunology
KW  -  Neurosciences
KW  -  Neurosciences & Neurology
KW  -  AMYLOID PRECURSOR PROTEIN
KW  -  MILD COGNITIVE IMPAIRMENT
KW  -  ALPHA-SECRETASE ADAM10
KW  -  HUMAN CEREBROSPINAL-FLUID
KW  -  TACE ACTIVITY
KW  -  BACE1 ACTIVITY
KW  -  DISINTEGRIN
KW  -  METALLOPROTEASE
KW  -  IDENTIFICATION
KW  -  DIMERIZATION
A1  - Sogorb-Esteve, A
A1  - Garcia-Ayllon, M-S
A1  - Gobom, J
A1  - Alom, J
A1  - Zetterberg, H
A1  - Blennow, K
A1  - Saez-Valero, J
ID  - discovery10056835
N2  - BACKGROUND:
The disintegrin metalloproteinase 10 (ADAM10) is the main ?-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, A?42, 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.
SN  - 1742-2094
PB  - BMC
UR  - https://doi.org/10.1186/s12974-018-1255-9
N1  - © 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.
TI  - Levels of ADAM10 are reduced in Alzheimer's disease CSF
EP  - 9
AV  - public
VL  - 15
Y1  - 2018/07/25/
ER  -