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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2015

Open Access 01-12-2015 | Research

Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls

Authors: Hlin Kvartsberg, Erik Portelius, Ulf Andreasson, Gunnar Brinkmalm, Konstantin Hellwig, Natalia Lelental, Johannes Kornhuber, Oskar Hansson, Lennart Minthon, Philipp Spitzer, Juan M Maler, Henrik Zetterberg, Kaj Blennow, Piotr Lewczuk

Published in: Alzheimer's Research & Therapy | Issue 1/2015

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Abstract

Introduction

Synaptic dysfunction and degeneration are central events in Alzheimer’s disease (AD) pathophysiology that are thought to occur early in disease progression. Synaptic pathology may be studied by examining protein biomarkers specific for different synaptic elements. We recently showed that the dendritic protein neurogranin (Ng), including the endogenous Ng peptide 48 to 76 (Ng48–76), is markedly increased in cerebrospinal fluid (CSF) in AD and that Ng48–76 is the dominant peptide in human brain tissue. The aim of this study was to characterize Ng in plasma and CSF using mass spectrometry and to investigate the performance of plasma Ng as an AD biomarker.

Methods

Paired plasma and CSF samples from patients with AD (n = 25) and healthy controls (n = 20) were analyzed in parallel using an immunoassay developed in-house on the Meso Scale Discovery platform and hybrid immunoaffinity-mass spectrometry (HI-MS). A second plasma material from patients with AD (n = 13) and healthy controls (n = 17) was also analyzed with HI-MS. High-resolution mass spectrometry was used for identification of endogenous plasma Ng peptides.

Results

Ng in human plasma is present as several endogenous peptides. Of the 16 endogenous Ng peptides identified, seven were unique for plasma and not detectable in CSF. However, Ng48–76 was not present in plasma. CSF Ng was significantly increased in AD compared with controls (P < 0.0001), whereas the plasma Ng levels were similar between the groups in both studies. Plasma and CSF Ng levels showed no correlation. CSF Ng was stable during storage at −20°C for up to 2 days, and no de novo generation of peptides were detected.

Conclusions

For the first time, to our knowledge, we have identified several endogenous Ng peptides in human plasma. In agreement with previous studies, we show that CSF Ng is significantly increased in AD as compared with healthy controls. The origin of Ng in plasma and its possible use as a biomarker need to be further investigated. The results suggest that CSF Ng, in particular Ng48–76, might reflect the neurodegenerative processes within the brain, indicating a role for Ng as a potential novel clinical biomarker for synaptic function in AD.
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Metadata
Title
Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls
Authors
Hlin Kvartsberg
Erik Portelius
Ulf Andreasson
Gunnar Brinkmalm
Konstantin Hellwig
Natalia Lelental
Johannes Kornhuber
Oskar Hansson
Lennart Minthon
Philipp Spitzer
Juan M Maler
Henrik Zetterberg
Kaj Blennow
Piotr Lewczuk
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-015-0124-3

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