Low density lipoprotein receptor-related protein and apolipoprotein E expression is altered in schizophrenia

Andrew Stuart Gibbons

doi:10.3389/fpsyt.2010.00019

Abstract

Our recent microarray study reported altered mRNA expression of several low density lipoprotein receptor-related proteins (LRP) associated with the first 4 years following diagnosis with schizophrenia. Whilst this finding is novel, apolipoprotein E (APOE), which mediates its activity through LRPs, has been reported by several studies to be altered in brains of subjects with schizophrenia. We used qPCR to measure the expression of LRP2, LRP4, LRP6, LRP8, LRP10 and LRP12 mRNA in Brodmann's area (BA) 46 of the dorsolateral prefrontal cortex in 15 subjects with short duration of illness schizophrenia (SDS) and 15 pair matched controls. We also used Western blotting to measure APOE protein expression in BA46 from these subjects. Amongst the LRPs examined, LRP10 expression was significantly increased (P = 0.03) and LRP12 was significantly decreased (P < 0.01) in SDS. APOE protein expression was also increased in SDS (P = 0.01). No other marker examined in this study was altered with diagnosis. Our data supports a role for distinct members of the LRP family in the pathology of schizophrenia and adds weight to the hypothesis that aberrant apolipoprotein signaling is involved in the early stages of schizophrenia.

Highlights

Our recent microarray study of gene expression in the dorsolateral prefrontal cortex from subjects with schizophrenia of short (SDS) (22 years) duration of illness schizophrenia and age and sex matched controls reported altered expression of several low density lipoprotein receptor-related proteins (LRP) associated with short duration of illness schizophrenia (SDS) (Narayan et al, 2008)
Our finding of increased Apolipoprotein E (APOE) protein expression in BA46 in subjects with SDS adds to previous findings of increased APOE protein expression associated with schizophrenia in BA46 and BA9 (Dean et al, 2003; Digney et al, 2005)
In our previous microarray study, we did not detect altered levels of APOE mRNA expression in SDS a subset (n = 8) of subjects used in this study (Narayan et al, 2008)

Summary

Introduction

Our recent microarray study of gene expression in the dorsolateral prefrontal cortex from subjects with schizophrenia of short (SDS) (22 years) duration of illness schizophrenia and age and sex matched controls reported altered expression of several low density lipoprotein receptor-related proteins (LRP) associated with SDS (Narayan et al, 2008). Levels of ApoE protein expression have been reported to be increased in subjects with schizophrenia (Dean et al, 2003; Digney et al, 2005). APOE expression is decreased in the periphery of subjects with schizophrenia (Dean et al, 2008) suggesting an underlying level of complexity in the regulatory dysfunction of this protein. This is further evidenced by conflicting published data regarding the association between APOE polymorphisms and the incidence of schizophrenia (Harrington et al, 1995; Martinoli et al, 1995; Thibaut et al, 1998; Lee et al, 2001)

Methods

Results

Conclusion