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J Neuroinflammation. 2018 Jul 25;15(1):213. doi: 10.1186/s12974-018-1255-9.

Levels of ADAM10 are reduced in Alzheimer's disease CSF.

Author information

1
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av. Ramón y Cajal s/n, Sant Joan d'Alacant, E-03550, Alicante, Spain.
2
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
3
Unidad de Investigación, Hospital General Universitario de Elche, Fundación para el Fomento de la Investigación Sanitaria Biomédica de la Comunidad Valenciana (FISABIO), Elche, Spain.
4
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
5
Department of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
6
Servicio de Neurología, Hospital General Universitario de Elche, Fundación para el Fomento de la Investigación Sanitaria Biomédica de la Comunidad Valenciana (FISABIO), Elche, Spain.
7
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
8
UK Dementia Research Institute at UCL, London, UK.
9
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av. Ramón y Cajal s/n, Sant Joan d'Alacant, E-03550, Alicante, Spain. j.saez@umh.es.
10
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain. j.saez@umh.es.

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.

PMID:
30045733
PMCID:
PMC6060469
DOI:
10.1186/s12974-018-1255-9
[Indexed for MEDLINE]
Free PMC Article

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