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BioMed Central, Alzheimer's Research and Therapy, 1(7), 2015

DOI: 10.1186/s13195-015-0124-3

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

Journal article published in 2015 by Hlin Kvartsberg ORCID, Erik Portelius, Ulf Andreasson, Gunnar Brinkmalm ORCID, Konstantin Hellwig, Natalia Lelental, Johannes Kornhuber ORCID, Oskar Hansson, Lennart Minthon, Philipp Spitzer, Juan M. Maler, Henrik Zetterberg, Kaj Blennow, Piotr Lewczuk
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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 (Ng 48–76 ), is markedly increased in cerebrospinal fluid (CSF) in AD and that Ng 48–76 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, Ng 48–76 was not present in plasma. CSF Ng was significantly increased in AD compared with controls ( P