X-Aptamer Technology Identifies C4A and ApoB in Blood as Potential Markers for Schizophrenia

Abstract

The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech­nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in plasma samples from schizophrenia patients (n = 60) compared to controls (n = 20). Using a combinatorial library of X-aptamer beads, we developed a two-color flow cytometer-based approach to identify specific X-aptamers that bound with high specificity to each target group. Based on this, we synthesized two unique X-aptamer sequences, and specific proteins pulled down from the patient and control groups by these X-aptamers were identified by mass spectrometry. We identified two protein biomarkers, complement component C4A and ApoB, upregulated in plasma samples from schizophrenia patients. ELISA validation suggested that the observed differences in C4 levels in patients are likely due to the presence of the illness itself, while ApoB may be a marker of antipsychotic-induced alterations. These studies highlight the utility of the X-aptamer technology in the identification of biomarkers for schizophrenia that will advance our understanding of the pathophysiological mechanisms of this disorder.

Peripheral complement proteins in schizophrenia: A systematic review and meta-analysis of serological studies

“…Ten studies reported C4 concentrations, of which two found significantly increased levels in cases ( Laskaris et al, 2018 ; Walss-Bass et al, 2019 ), one found significantly decreased levels in cases ( Ji et al, 2019 ) and seven studies found no significant difference ( Ali et al, 2017 ; Fontana et al, 1980 ; Idonije et al, 2012 ; Maes et al, 1997 ; Santos Soria et al, 2012 ; Spivak et al, 1993 ; Spivak et al, 1989 ). One of these studies stratified cases by medication status ( Maes et al, 1997 ) and found increased serum C4 in drug-free patients compared to controls without schizophrenia ( Maes et al, 1997 ).…”

“…Thirty-four articles were excluded for multiple reasons (detailed in Fig. 1 ) resulting in 24 included studies ( Ali et al, 2017 ; Boyajyan et al, 2010 ; Cazzullo et al, 1998 ; Foldager et al, 2012 ; Fontana et al, 1980 ; Hakobyan et al, 2005 ; Hong et al, 2016b ; Idonije et al, 2012 ; Ji et al, 2019 ; Kucharska-Mazur et al, 2014 ; Laskaris et al, 2018 ; Li et al, 2016 ; Li et al, 2012 ; Maes et al, 1997 ; Mayilyan et al, 2006 ; Mayilyan et al, 2008a ; Ramsey et al, 2013 ; Santos Soria et al, 2012 ; Sasaki et al, 1994 ; Schwarz et al, 2012 ; Spivak et al, 1993 ; Spivak et al, 1989 ; Walss-Bass et al, 2019 ; Wong et al, 1996 ).

Fig.

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“…In the majority of included studies assays were performed using serum samples; five studies instead used plasma ( Hong et al, 2016b ; Kucharska-Mazur et al, 2014 ; Li et al, 2016 ; Maes et al, 1997 ; Walss-Bass et al, 2019 ). Thirteen studies recruited inpatient cases ( Boyajyan et al, 2010 ; Fontana et al, 1980 ; Hakobyan et al, 2005 ; Hong et al, 2016b ; Idonije et al, 2012 ; Ji et al, 2019 ; Li et al, 2016 ; Maes et al, 1997 ; Sasaki et al, 1994 ; Schwarz et al, 2012 ; Spivak et al, 1993 ; Spivak et al, 1989 ; Wong et al, 1996 ), seven studies recruited outpatients ( Ali et al, 2017 ; Laskaris et al, 2018 ; Li et al, 2012 ; Mayilyan et al, 2006 ; Mayilyan et al, 2008a ; Santos Soria et al, 2012 ; Walss-Bass et al, 2019 ), one recruited both inpatient and outpatient cases ( Foldager et al, 2012 ) and in the remainder the hospitalisation status of patients was not determined ( Cazzullo et al, 1998 ; Kucharska-Mazur et al, 2014 ; Ramsey et al, 2013 ). In many studies, the clinical status of patients at the time of blood sampling (i.e.…”

“…For C4, sufficient data were available to perform meta-analysis of ten studies ( Ali et al, 2017 ; Fontana et al, 1980 ; Idonije et al, 2012 ; Ji et al, 2019 ; Laskaris et al, 2018 ; Maes et al, 1997 ; Santos Soria et al, 2012 ; Spivak et al, 1993 ; Spivak et al, 1989 ; Walss-Bass et al, 2019 ). In one study ( Idonije et al, 2012 ) data for cases were presented stratified by stage of illness (chronic vs. FEP) and the two groups were compared separately to the same group of healthy controls.…”

The Plasma Peptides of Alzheimer’s Disease

“…Plasma levels of Complement 4a protein are increased in Alzheimer's disease [19]. X-Aptamers identi ed C4A and ApoB as potential markers for schizophrenia from blood [20]. Complement and microglia cells of the innate immune system mediate early synapse loss in a mouse model of Alzheimer's dementia [21].…”