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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2015

Open Access 01-12-2015 | Research article

Heteromers of amyloid precursor protein in cerebrospinal fluid

Authors: Inmaculada Cuchillo-Ibañez, Inmaculada Lopez-Font, Alba Boix-Amorós, Gunnar Brinkmalm, Kaj Blennow, Jose-Luis Molinuevo, Javier Sáez-Valero

Published in: Molecular Neurodegeneration | Issue 1/2015

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Abstract

Background

Soluble fragments of the amyloid precursor protein (APP) generated by α- and β-secretases, sAPPα and sAPPβ, have been postulated as promising new cerebrospinal fluid (CSF) biomarkers for the clinical diagnosis of Alzheimer’s disease (AD). However, the capacity of these soluble proteins to assemble has not been explored and could be relevant. Our aim is to characterize possible sAPP oligomers that could contribute to the quantification of sAPPα and sAPPβ in CSF by ELISA, as well as to characterize the possible presence of soluble full-length APP (sAPPf).

Results

We employed co-immunoprecipitation, native polyacrylamide gel electrophoresis and ultracentrifugation in sucrose density gradients to characterize sAPP oligomers in CSF. We have characterized the presence of sAPPf in CSF from NDC and AD subjects and demonstrated that all forms, including sAPPα and sAPPβ, are capable of assembling into heteromers, which differ from brain APP membrane-dimers. We measured sAPPf, sAPPα and sAPPβ by ELISA in CSF samples from AD (n = 13) and non-disease subjects (NDC, n = 13) before and after immunoprecipitation with antibodies against the C-terminal APP or against sAPPβ. We demonstrated that these sAPP heteromers participate in the quantification of sAPPα and sAPPβ by ELISA. Immunoprecipitation with a C-terminal antibody to remove sAPPf reduced by ~30% the determinations of sAPPα and sAPPβ by ELISA, whereas immunoprecipitation with an APPβ antibody reduced by ~80% the determination of sAPPf and sAPPα.

Conclusions

The presence of sAPPf and sAPP heteromers should be taken into consideration when exploring the levels of sAPPα and sAPPβ as potential CSF biomarkers.
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Metadata
Title
Heteromers of amyloid precursor protein in cerebrospinal fluid
Authors
Inmaculada Cuchillo-Ibañez
Inmaculada Lopez-Font
Alba Boix-Amorós
Gunnar Brinkmalm
Kaj Blennow
Jose-Luis Molinuevo
Javier Sáez-Valero
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-10-2

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